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ABSTRACT: Estimation of nutritional needs in burn patients is difficult. In 24 severely burned patients, we measured CO2 production and O2 consumption continuously during their period of mechanical ventilation.
Patients with extensive burns were placed on a continuous metabolic monitor (CMM) (Puritan Bennett Co., Kingwood, TX), and metabolic expenditure was recorded each 24 hours. High protein enteral feedings were started within several hours of admission, and administration rates were adjusted to meet daily caloric demands as determined by the CMM. Full-thickness wounds were excised as early as patient condition permitted, and wounds were closed with autograft, allograft, or TransCyte (Advanced Tissue Sciences Inc., La Jolla, CA). Daily 24-hour caloric needs as measured by CMM were compared with baseline caloric needs predicted by the Harris-Benedict equation and also compared with actual daily caloric intake. Patients were removed from study when they were off continuous mechanical ventilation.
A total of 24 patients were studied, with a mean age of 46 years and a 44% total body burn size (partial- and full-thickness). All full-thickness burns were completely excised by a mean of 6.5 days postburn. Mean daily energy expenditures remained elevated through the duration of the study period (42 days), with a mean elevation of 184.9% of baseline as predicted by Harris-Benedict equation. Patients received enteral feedings, which met 99.4% of actual caloric needs as predicted by CMM during the study period.
Continuous metabolic monitoring demonstrates that early wound excision and wound closure, coupled with aggressive enteral nutritional support with high protein formulas, do not prevent the marked hypermetabolism that accompanies thermal injury.
The Journal of trauma 11/2000; 49(4):667-71; discussion 671-2. · 2.48 Impact Factor
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ABSTRACT: Wound healing is a sequential biological process that involves the integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes, and remodeling of the scar, all of which are regulated by specific soluble mediators. To modulate wound healing specific mediators have to be identified and functionally characterized. Therefore we addressed this study on the polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its function in epidermal wound healing.
Peptide purification, bioassays for PMN chemotaxis, and sequential IL-8 measurements were performed on human wound fluid from burn blisters and skin graft donor sites. Histology for IL-8 immunoreactivity was included. In vitro human keratinocytes were assayed for proliferation, migration, and integrin expression after IL-8 treatment. Wounding experiments with topical IL-8 were performed in a chimeric mouse model.
IL-8 was found to be the major bioactive chemoattractant for PMNs in human blister and skin graft donor site wound fluids (mean levels ranging from 173 ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released intracellular epidermal IL-8 immunoreactivity at the wound edge was considered as an immediate source of IL-8 while NH(2)-terminal analysis revealed the 77-amino-acid residue form as a second source of IL-8 possibly PMN derived. In vitro experiments on the effect of recombinant human (rh) IL-8 on keratinocyte proliferation revealed a rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml), which was accompanied by an increase in cells in S phase and overexpression of the integrin subunit alpha6. In vivo topically applied IL-8 (1 microg/ml) on human skin grafts in a chimeric mouse model enhanced reepithelialization in IL-8 treated animals over controls due to elevated numbers of mitotic keratinocytes. Wound contraction was significantly diminished by topical IL-8.
These results indicate the sequential function of endogenous IL-8 in all phases of human wound healing. Topical IL-8 may be useful in impaired wound healing.
Journal of Surgical Research 10/2000; 93(1):41-54. · 2.25 Impact Factor
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ABSTRACT: Keratinocyte migration over the wound bed is the single most important parameter for wound epithelialization. Therefore, improvement of the wound bed matrix holds considerable promise for the shortening of hospitalization time in patients with ulcers, burns, and chronic wounds. We investigated wound epithelialization in athymic mice in the presence or absence of a sheet of cultured human fibroblasts. The physiology of keratinocyte growth on fibroblast sheets was investigated in tissue culture using histology, immunofluorescence, and electron microscopy. Keratinocytes from human skin explants were unable to attach or migrate on full-thickness dorsal wounds of athymic mice. Placement of a fibroblast-seeded polyglactin mesh on the wounds resulted in dramatically increased keratinocyte outgrowth. Similarly, human keratinocytes showed good outgrowth on fibroblast sheets at the air/liquid interface in tissue culture. Outgrowth was correlated inversely with fibroblast viability, indicating that the observed effect was due to the complex extracellular matrix secreted by the fibroblasts and matrix-bound growth factors rather than ongoing growth factor release. Collagen IV, a promoter of keratinocyte migration, was found to be abundant in the fibroblast-derived matrix. This study demonstrates that wounds which are unable to support keratinocyte migration can undergo epithelialization if a conducive substrate, supplying appropriate extracellular matrix and/or matrix-bound growth factors, is applied.
Tissue Engineering 12/1999; 5(6):555-62. · 4.02 Impact Factor
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Pediatrics in Review 05/1999; 20(4):117-23; quiz 124. · 0.55 Impact Factor
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ABSTRACT: Diaspirin crosslinked hemoglobin (DCLHb; Baxter Healthcare Corp, Deerfield, IL) is hemoglobin-based oxygen carrier which, in our laboratory, improved hemodynamic parameters in a rat burn shock model. Our objective was to compare the effects on hemodynamic parameters and metabolic acidosis of resuscitation with different doses of fresh blood (FB) vs DCLHb. Male Wistar rats (200 to 250 g), surgically prepared for an acute study, were randomly assigned to one of five treatment groups. (n = 8): I. SHAM (not burned, not resuscitated), II. DCLHb 2 ml/kg/% Total Body Surface Area (TBSA) burn and 2 ml/kg/% TBSA burn of Lactated Ringers (LR), III. DCLHb 1 ml/kg/% TBSA burn and 1 ml/kg/% TBSA burn of LR IV. FB 2 ml/kg/% TBSA burn and 2 ml/kg/% TBSA burn of LR V. FB 1 ml/kg/% TBSA burn and 1 ml/kg/% TBSA burn of LR After placement of indwelling catheters, the following baseline hemodynamic values were obtained mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR) and base excess (BE). The animals were immediately intravenously resuscitated after receiving a 30% scald burn and were followed for 6 hours. Resuscitation was based on the Parkland formula. Blood was obtained from donor male Wistar rats. The animals were euthanized at 6 hours. MAP remained within normal range in all groups. The SVR, CO, SV and BE were normalized earlier in the LR-DCLHb groups when compared to the LR-FB groups (p < 0.05). Early resuscitation with DCLHb is superior to FB in improving hemodynamics in this model. There appears to be a direct relationship between dose and effect with the use of DCLHb. DCLHb could be useful in decreasing resuscitation fluid requirements in acute burns without compromising general tissue perfusion.
Artificial Cells Blood Substitutes and Biotechnology 04/1999; 27(2):135-52. · 0.98 Impact Factor
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ABSTRACT: Diaspirin cross-linked hemoglobin (DCLHb) is a vasoactive hemoglobin-based oxygen carrier or "blood substitute" that has been shown to improve base deficit in several experimental studies of hemorrhagic shock. Our objective was to determine if the addition of DCLHb to the resuscitation regimen would improve hemodynamic parameters, metabolic acidosis, and survival in our rat burn shock model compared with currently used resuscitation therapy.
This was a randomized, controlled, experimental rat study. Male Wistar rats, weighing 200 to 250 g, were surgically prepared for an acute study. After placement of indwelling catheters, baseline hemodynamic values (mean arterial pressure, cardiac output, systemic vascular resistance, stroke volume, and base excess) were obtained. Thirty-two rats were used in the study, and they were either subjected to a 30% scald burn (experimental group) or sham burned (control group). The experimental animals were immediately intravenously resuscitated and followed for 6 hours. The resuscitation was based on the Parkland formula (4 mL/kg for each 1% of total body surface area [TBSA] burn), with 50% of the calculated fluid amount to be administered at a constant rate during the first 8 hours after burn. The animals were resuscitated for 6 hours and received between 9.00 and 11.25 mL of fluid depending on weight. The experimental animals were randomly assigned to one of three treatment groups: group I, lactated Ringer's solution; group II, lactated Ringer's solution-human serum albumin; group III, lactated Ringer's solution-DCLHb. Group I (n = 8) received 4 mL/kg lactated Ringer's solution for each 1% of TBSA burn. Group II (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg human serum albumin for each 1% of TBSA burn. Group III (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg DCLHb for each 1% of TBSA burn. The sham group (n = 8) was not burned and was not resuscitated. Animals that survived up to 6 six hours were killed.
We found that mean arterial pressure, cardiac output, stroke volume, and base excess were all improved in the DCLHb-lactated Ringer's solution-treated animals compared with the other experimental treatment groups. The 6-hour mortality rates were zero of eight (lactated Ringer's solution-DCLHb group), zero of eight (sham group), three of eight (lactated Ringer's solution-human serum albumin group), and six of eight (lactated Ringer's solution only group).
Early resuscitation with DCLHb is superior to non-oxygen-carrying resuscitative fluids in improving hemodynamics and survival in this model of burn shock. DCLHb might improve general tissue perfusion in the acute postburn period, and it could be useful in the early management of patients with severe burns.
The Journal of trauma 03/1999; 46(2):286-91. · 2.48 Impact Factor
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J F Hansbrough
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ABSTRACT: Early and continued nutritional support has been determined to be an important component of therapy for seriously burned patients. The hypermetabolic response to severe injury requires increased calorie and protein intake to blunt the catabolism and loss of lean muscle mass. Enteral feeding has been found to directly nourish the gastrointestinal tract and may help reverse the defective gut barrier which accompanies burn shock. In contrast, intravenous nutritional support appears to lack effectiveness in burn patients and may actually increase morbidity and mortality.
Gastrointestinal Endoscopy Clinics of North America 08/1998; 8(3):645-67.
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ABSTRACT: There is much progress to be made to optimize the development of laboratory-grown temporary and permanent skin replacements. Replacement of both epidermal and dermal layers is important for achieving optimal take of cultured grafts and for optimizing the quality of wound healing. Although the use of retained cadaver allodermis on the wound bed may improve the performance of cultured epithelium, the development of successful, complete dermal-epidermal skin replacements (composite grafts) would greatly simplify burn management. In the future, handling and stability of the cultured grafts should be improved, and clinical outcomes should be expected to be superior. Unfortunately, funding for this type of applied research has not achieved high priority from the federal government granting agencies, despite the great clinical need for improved technology. Future progress depends largely upon commercial support.
Clinics in Plastic Surgery 08/1998; 25(3):407-23. · 1.42 Impact Factor
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ABSTRACT: Melanoma growth stimulatory activity/gro alpha (MGSA), a member of the alpha-chemokine family, is produced by a variety of dermal and epidermal cells and can act in a paracrine and autocrine fashion. However, little is known about the importance of MGSA in wound healing. In this study, we quantified the levels of MGSA protein in burn blister and donor site wound fluids. We studied the effects of MGSA on proliferation and migration of primary human keratinocytes and modulation of their integrin expression. Blister fluids contained 0.79 ng/ml (range 0.018 to 4.86 ng/ml) MGSA. Substantial increasing amounts of MGSA were found in donor site fluids from day 1 through day 5 with mean levels ranging from 1.77 to 103 ng/ml at postoperative day 5, which correlated with increasing amounts of tumor necrosis factor alpha (r = 0.86), a known stimulus for MGSA production. In vitro proliferation experiments revealed a maximum stimulation (2.6-fold) with 10 ng/ ml MGSA for 7 days over unstimulated keratinocyte controls; the ED50 was 0.2 ng/ml. DNA content analysis revealed an increase in S phase with 10 ng/ml MGSA stimulation. In cultured keratinocytes, MGSA enhanced the mean fluorescence intensity for alpha 6, while no significant change was seen for beta 1, alpha 2 and alpha 5. We also studied the effect of topically applied MGSA (50 ng/cm2) on the healing of meshed split-thickness human skin grafts on athymic mice. In these wounds, MGSA stimulated the rate of epithelialization (P < 0.05) at day 7, and an increased proportion of mitotic keratinocytes was observed. Wound contraction was significantly (P < 0.05) reduced on days 7 and 14 in the MGSA-treated group. These results suggest that MGSA participates in wound healing by stimulating keratinocyte proliferation.
Archives for Dermatological Research 04/1997; 289(4):204-12. · 2.28 Impact Factor
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ABSTRACT: Neutrophil deposition in tissues (leukosequestration) after shock may produce local tissue injury from proteases and high-energy oxygen species released from sequestered neutrophils. The initial step in the binding of neutrophils to capillary endothelium is the interaction of adhesion molecule (selectin) receptors between neutrophils and endothelial cells. We quantified leukosequestration in the tissues of burned rats using two methods of analysis: a) measurement of lung myeloperoxidase; and b) measurement of radiolabeled neutrophils and erythrocytes deposited in multiple tissues. We then determined the ability of a selectin receptor blocking agent to affect neutrophil deposition in tissues after burn injury.
Prospective, controlled, laboratory study.
University research laboratory.
Male Wistar rats (200 to 300 g).
After tracheostomy and venous cannulation, rats received 17% total body surface area full-thickness contact burns and were resuscitated with saline (20 mL i.p.). Experimental animals received 2 mg/kg body weight i.v. administration of a P- and E-selectin blocking monoclonal antibody, CY-1747, immediately after burn. Lung tissue neutrophils were estimated by measuring myeloperoxidase in lung tissue. Neutrophil retention in lung, liver, spleen, gut, skin, muscle, kidney, and brain tissues was determined by removing (preburn) and differentially radiolabeling neutrophils (111In) and erythrocytes (51Cr), reinfusing cells 4.5 hrs after burn, and measuring tissue radioactivity 30 mins later. Edema was estimated by measuring extravasated 125 I-labeled albumin in the various tissues. Peripheral blood neutrophils were analyzed for intracellular hydrogen peroxide content, utilizing a fluorescent dye that reacts with hydrogen peroxide, coupled with analysis of cell fluorescence by flow cytometry.
Myeloperoxidase concentration was increased in lungs 5 hrs after burn (p < .05), indicating neutrophil deposition. Radioisotope studies demonstrated significant (p < .05) leukosequestration into the lung, gut, kidney, skin, and brain tissues at 5 hrs after burn. Flow cytometry showed increased intracellular hydrogen peroxide content in peripheral blood neutrophils 5 hrs after burn. Tissue edema, manifested by radiolabeled albumin retention, was not seen in any tissues. Postburn neutrophil deposition in lungs and liver was blocked (p < .05) by administration of CY-1747 after burn, but maximal neutrophil hydrogen peroxide content was unaffected.
Burn injury in rats results in accumulation of neutrophils in multiple tissues. Neutrophil deposition in the lungs and liver is blocked by administration of the E/P-selectin blocking antibody, CY-1747. Since sequestration of metabolically active neutrophils may induce tissue injury, therapies that block postburn leukosequestration may improve clinical outcomes by limiting remote tissue injury.
Critical Care Medicine 09/1996; 24(8):1366-72. · 6.33 Impact Factor
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ABSTRACT: Burn excision followed by immediate wound coverage has become the clinical standard for managing extensive burn injuries in much of the world. When sufficient autograft skin to achieve permanent wound closure is unavailable, cell culture technology has made the use of cultured human keratinocyte (HK) sheets clinically feasible. Whereas previous techniques have focused on development of multilayered, differentiated HK sheets, our attention has been drawn to using HK in a highly proliferative, less differentiated state. Time requirements for preparation of multistratified cultured HK are high, and preparatory steps may destroy important integrin adhesion molecules.
We describe the use of HK cultured to single layer confluence on a polyurethane membrane(HD), with serum-free medium. HK-HD grafts were transplanted to full-thickness wounds on athymic mice (n = 31). A second group of mice (DG-HK-HD), n = 28) received a living human dermal replacement containing cultured fibroblasts before placement of HK-HD. Control mice received HD alone (n = 4). Basement membrane proteins on healed wounds and surface integrins on cultured HK were identified by means of immunostaining and direct microscopic visualization.
HK cultured just to the confluent state on polyurethane membrane were positive for integrins alpha(5) and alpha(6), major integrins on proliferating HK. Histologic analysis showed epithelialized wounds in all groups after 21 days. Using an anti-human involucrin antibody we demonstrated the presence of HK in 64.5% of the HK-HD group, 61% of the DG-HK-HD group, and 0% in the HD group. Mice that received the living human dermal replacement containing cultured fibroblasts in combination with HK-HD grafts developed a thick, well-vascularized neodermis. Strong laminin and collagen IV staining was observed in wound areas covered with HK.
These data show that full-thickness wounds can be closed by application of a single layer of proliferating HK cultured on a biocompatible polyurethane membrane. This technique is an alternative to the use of multilayered, differentiated HK sheets. Preparation times for HK-HD grafts should be significantly shorter than required for multilayered HK sheets, technical efforts should be less, and more extensive wound areas could be covered.
Surgery 08/1996; 120(1):16-22. · 3.10 Impact Factor
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Plastic & Reconstructive Surgery 06/1996; 97(6):1312-3. · 3.38 Impact Factor
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ABSTRACT: Current tissue-culture techniques permit the rapid expansion of keratinocyte populations, such that an area of cultured epithelium equivalent to that of the surface of an adult can be obtained from an initial small skin biopsy. Unfortunately, technical obstacles have delayed the widespread clinical use of multilayered sheets of epithelium. These factors include difficulties in preparing and transferring fragile cultured epithelial sheets, as well as frequent unsatisfactory "take" of cultured grafts on the wound bed. As greater understanding of the complex interactions of cells and matrix evolves, so have new techniques in the field of cultured keratinocytes for grafting. We have utilized an animal model that allows us to examine some of these new methods and the factors which influence graft take. It has become clear that adhesion properties of keratinocytes, early delivery of proliferative keratinocytes to the wound, the development of dermal replacements, and improved delivery systems for keratinocytes are important factors which must be considered for the optimal provision of skin replacements.
Journal of Surgical Research 06/1996; 62(2):288-95. · 2.25 Impact Factor
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ABSTRACT: Neutrophil (PMN) deposition in tissues (leukosequestration) after shock may produce local tissue injury from proteases and oxygen intermediaries which are released from sequestered PMNs. We quantified leukosequestration in tissues in burned rats using two methods of analysis: 1), measurement of lung myeloperoxidase (MPO); 2), measurement of radiolabeled PMNs and erythrocytes deposited in multiple tissues. After tracheostomy and venous cannulation, rats received 17% TBSA full-thickness contact burns and were resuscitated with 20 cc intraperitoneal saline. Lung PMNs were estimated by measuring MPO in lung tissue. PMN influx into lung, liver, spleen, gut, skin, muscle, kidney, and brain was determined by removing (preburn) and differentially radiolabeling PMNs (111In) and erythrocytes (51Cr), reinfusing cells 4.5 hr postburn, and measuring tissue radioactivity 5 hr postburn. Tissue edema was measured by determining extravasation of 125I-labeled albumin in tissues. Peripheral blood PMNs were analyzed for intracellular H2O2 content utilizing a fluorescent dye which reacts with H2O2 coupled with analysis of cell fluorescence by flow cytometry. MPO was elevated in lungs 8 hr postburn (P < 0.05). PMN influx into lung tissues was confirmed by histologic examination. Radioisotope studies demonstrated significant (P < 0.05) leukosequestration into lung, gut, kidney, skin, and brain tissues at 5 hr postburn. Respiratory burst activity of peripheral blood PMNs was increased 5 hr postburn (P < 0.05). Flow cytometric analysis indicated that peripheral blood PMNs were capable of producing markedly increased H2O2 levels 5 hr postburn. Tissue edema, manifested by radiolabeled albumin influx, was not seen in any tissues. Since others have shown that sequestration of metabolically active PMNs may induce remote tissue injury, therapies which block postburn leukosequestration may be able to improve clinical outcomes by limiting remote tissue injury.
Journal of Surgical Research 02/1996; 61(1):17-22. · 2.25 Impact Factor
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ABSTRACT: Tissue myeloperoxidase (MPO) is a marker of neutrophil (PMN) accumulation in tissues (leukosequestration). We measured MPO in the livers, guts, and lungs of mice after burn injury and studied the additive effect of burn excision on lung MPO. Lung histologic characteristics were also examined. PMN respiratory activity was assessed by measuring intracellular H2O2 content.
Mice received 32% total body surface area (TBSA) burns; some underwent burn excision followed by wound closure with allograft skin, either immediately or 48 hours after burn. Tissue MPO was measured by a colormetric assay, and intracellular H2O2 was quantified by flow cytometry.
MPO was elevated in lungs 8 to 24 hours after burn (p < 0.05) but not in the liver or ileum. Other burned mice received either immediate or 48-hour-delayed wound excision and allografting. In controls a similar-size area was excised and grafted with normal or burned skin. Burned animals had increased lung MPO compared with nonburned animals (p < 0.05). Highest lung MPO levels were seen after burn/immediate excision (p < 0.001). Lung MPO levels were not different comparing unburned mice undergoing skin excision and grafting with either nonburned or burned skin. When burn excision was delayed 48 hours, lung MPO was increased moderately (p < 0.05) but remained far below levels in mice that were excised immediately after burn. PMN influx into lung tissues was confirmed by histologic examination. PMN H2O2 production was increased in burned mice and was additionally increased after immediate wound excision.
Although burn injury produces pulmonary leukosequestration, the phenomenon is unrelated to local effects of burned skin. In this experimental model immediate postburn wound excision increased pulmonary leukosequestration to higher levels than after burn injury alone, and intracellular H2O2 content also increased. Pulmonary leukosequestration may predispose to lung injury, possibly limiting the benefits of wound excision performed extremely early postburn.
Surgery 11/1995; 118(5):884-92. · 3.10 Impact Factor
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ABSTRACT: Standard murine burn models include the administration of intraperitoneal (i.p.) saline solutions which are intended to resuscitate the animals during subsequent burn shock. Prehospital administration of small volumes of concentrated salt solutions has been recommended for the early treatment of haemorrhagic shock, and have also been utilized for burn shock. We studied the effects of bolus intravenous (i.v.) hypertonic saline (HS) or hypertonic saline/dextran-40 (HS + DEX) on animal survival and acid-base balance following 25 per cent total body surface area, full-thickness burn injury in mice. I.v. injections were administered via a tail vein immediately prior to burn injury. Some mice received 1 ml i.p. normal saline (NS) immediately after burn injury. Acid-base balance of vena caval blood was measured during the period of maximal metabolic acidosis following burn injury (12 h postburn). Preburn i.v. administration of 5 ml/kg of HS or HS+DEX, followed by 1 ml i.p. NS, only slightly decreased the degree of metabolic acidosis compared to animals receiving i.p. fluid alone, the standard resuscitation regimen for burned mice. Preburn i.v. administration of 0.2 ml volumes of HS or HS + DEX, without i.p. fluid administration, resulted in extremely high mortality. Immediate preburn i.v. administration of HS or HS + DEX did not eliminate metabolic acidosis in this murine burn model, and markedly increased the mortality when subsequent i.p. fluids were not administered. The degree of metabolic acidosis in the murine experimental burn model has not previously been clearly described. Furthermore, adequate fluid resuscitation of these animals may be difficult to achieve without indwelling vascular catheters which could deliver continuous i.v. fluids following burn injury.
Burns 06/1995; 21(3):185-90. · 1.96 Impact Factor
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ABSTRACT: Systemically administered antibiotic agents are not evenly distributed in the body, which frequently results in subtherapeutic regional drug concentrations, particularly in areas of poor vascularization, including wound sites. We have developed a lipid-based drug delivery system to provide prolonged levels of gentamicin in local tissues after local administration. Multivesicular liposomes are microspheres composed of lipid bilayer membranes surrounding multiple aqueous compartments that can contain drug. The preparation may be effective for the prevention and treatment of a variety of infections, including infections associated with indwelling vascular catheters.
Prospective, randomized trial.
Animal laboratory.
Mice, 6 to 12 wks of age, weighing 20 to 30 g.
We administered 0.5 mg of gentamicin encapsulated in multivesicular liposomes to dorsal subcutaneous tissue in mice. Animals were inoculated with 10(5) to 10(7) colony-forming units (cfu) of Staphylococcus aureus 2, 4, 6, and 8 days later. The cfu/g of tissue values were determined 2 days after inoculation.
With a 10(7) cfu challenge, animals that received 2- and 4-day pretreatment with multivesicular liposome/gentamicin had a 4 log10 reduction in cfu/g of tissue compared with controls. When 10(5) cfu of Staphylococcus aureus were inoculated after 2- and 4-day pretreatment with multivesicular liposome/gentamicin, a 6 log10 reduction in bacteria colony-forming units was observed.
Local injection of multivesicular liposome/gentamicin provides sustained drug concentrations in regional tissues that protect against a massive bacterial challenge for at least four subsequent days.
Critical Care Medicine 02/1995; 23(1):84-91. · 6.33 Impact Factor
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ABSTRACT: Hyperbaric oxygen (HBO) is used but unproven for many conditions, including burns. We hypothesized that HBO therapy might increase oxygen delivery to intestine during burn shock and decrease mucosal injury.
University research laboratory.
We studied the effects of HBO therapy (100% oxygen at 2.4 atm absolute) on mesenteric bacterial colonies (MBCs) in mice following 32% total body surface area burns. MBCs were counted 24 or 48 hours postburn by culturing mesenteric tissue. Intestinal histologic features were examined, acid-base balance was measured, and pulmonary neutrophil deposition was estimated by lung myeloperoxidase content.
HBO delivered in a compression chamber.
Numbers of mice with MBCs.
With twice-daily HBO treatments, each treatment lasting 1.5 or 2 hours, fewer burned mice had MBCs. Three HBO treatments within 24 hours produced seizures, death, and increased numbers of mice with MBCs. Numbers of mice with MBCs were not influenced when compressed air (2.4 atm absolute) or 100% oxygen (1 atm absolute) was used. Villus histologic findings showed less damage in burned mice that received HBO therapy than in controls. Metabolic acidosis was not affected by HBO therapy, nor were lung myeloperoxidase levels.
HBO therapy was associated with reduced numbers of mice with MBCs after burn injury and reduced histologic evidence of mucosal damage, but lung myeloperoxidase levels and metabolic acidosis were not affected. HBO therapy may increase oxygen delivery to ischemic intestine and improve cellular metabolism; alternatively, increased tissue oxygen may augment killing of translocated bacteria by phagocytic cells. HBO deserves further investigation for burn treatment, but because of the narrow therapeutic window and continued neutrophil sequestration in the lungs, we should proceed cautiously.
Archives of Surgery 01/1995; 129(12):1338-42. · 4.24 Impact Factor
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ABSTRACT: Skin substitutes composed of cultured keratinocytes with or without a dermal substrate are now being used in the treatment of burns and other cutaneous wounds. Composite skin cultures (Graftskin, LSE), consisting of epidermal keratinocytes seeded on a fibroblast-containing collagen matrix and maintained at the air-liquid interface, develop a well differentiated epidermis in vitro with many of the morphological and biochemical features of intact skin. Basement membrane-associated antigens, developing hemidesmosomes and short segments of lamina densa are present at the dermal-epidermal junction in vitro, although the LSE lacks a continuous basement membrane. As epidermal differentiation proceeds, the culture develops a stratum corneum composed of electron-dense corneocytes surrounded by extracellular lipid. However, the intercorneocyte lipid lamellae do not exhibit the repeating pattern of broad and narrow electron lucent bands observed in electron micrographs of the stratum corneum of intact skin. In this study, LSE were grafted onto full thickness wounds in athymic mice. Animals were killed 6, 15, 30 and 60 d after surgery for examination by light and electron microscopy to identify any ultrastructural changes which occurred in the culture in response to the host environment. The grafted LSE integrated well into the host tissue and remained intact throughout the 60 d study period. At the dermal-epidermal junction, a continuous basement membrane with a well defined lamina densa was established by 15 d after surgery. An extensive network of anchoring fibrils was present by 30 d after surgery. Collagen fibrils within the dermal matrix condensed by 6 d after surgery and began organising into loosely packed bundles by 15 d after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Anatomy 11/1994; 185 ( Pt 2):325-33. · 2.37 Impact Factor
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Burns 07/1994; 20(3):282. · 1.96 Impact Factor
