Differential effects of a gram-negative and a gram-positive infection on autogenous and prosthetic grafts.

A canine model was developed to study the differential response of a gram-negative and a gram-positive bacterial infection on autogenous and prosthetic grafts. After replacing segments of the femoral arteries of 15 dogs with autogenous vein in one groin and polytetrafluoroethylene in the contralateral groin, 10(8) colony-forming units of nonmucin-producing Staphylococcus epidermidis (five dogs), Pseudomonas aeruginosa (five dogs), or sterile saline solution (five dogs) were directly inoculated onto the grafts. The grafts were examined 7 to 10 days after implantation. None of the control dogs exhibited inflammatory signs, and no grafts or anastomoses disrupted. S. epidermidis was unrecoverable from either graft material in any of the animals, although histologic evaluation confirmed neutrophils and bacteria in four of five animals in the vein and polytetrafluoroethylene groups. No dog inoculated with S. epidermidis had graft or anastomotic disruption. By contrast, P. aeruginosa was recovered from both types of grafts in all inoculated animals. Neutrophils, bacteria, and microabscesses were observed in all of these animals. In addition, three of five polytetrafluoroethylene grafts and all five vein grafts disrupted either at the anastomoses or in the body of the vein graft. Therefore S. epidermidis is a less virulent organism that may persist in graft walls despite negative cultures, whereas P. aeruginosa is a highly virulent organism that can disrupt native artery, vein grafts, and anastomoses. The graft material appears to be less important than the bacteria in determining the outcome of infection.

Repigmentation after burn injury in the guinea-pig.

The normal process of repigmentation of small partial- and full-thickness burn wounds in the guinea-pig has been studied visually, and by light microscopy and transmission electron microscopy of biopsy material, at various stages of healing. Repigmentation proceeded apace with re-epithelialization and occurred progressively from the periphery to the centre of the wound or scar. There was an initial lag period of 1 to 2 weeks post burn during which the melanocytes and melanin content of the regenerated epithelium were below or around normal control levels. Thereafter, the melanocytes and melanin were above normal levels and correlated with hyperpigmentation of the scar epithelium. Electron microscopy at 6 and 7 weeks post burn also confirmed the increased melanogenic and cytochrine activity of the melanocytes during this phase of burn healing.

Mafenide acetate concentrations and bacteriostasis in experimental burn wounds treated with a three-layered laminated mafenide-saline dressing.

A laminated wound dressing was developed to deliver mafenide acetate to granulating wounds. This study, using mafenide acetate cream (11.2%) and isotope dilution of 14C-labeled mafenide, has established the peak concentration and decay time for mafenide in the saline layer over the wound. Pseudomonas inhibition under identical concentrations was studied. Peak concentrations of 1,200 mg per deciliter of saline were observed after 2 hours. These levels decayed to 400 mg after 10 hours. Remoistening the dressing was required to achieve the peak and duration just mentioned. Pseudomonas inhibition of 88% of discs was present at 1,200, 800, and 700 mg concentrations. This dropped to 44% at 550 mg and 0 at 400 mg. The effective anti-Pseudomonas period was, therefore, 6 hours.

The "Sulfamylon sandwich"--a laminated mafenide-saline dressing.

Though commercially available 11.2% mafenide acetate cream (Sulfamylon) has been shown to be very effective in preventing burn wound sepsis, it has several serious drawbacks. Five percent mafenide acetate solution dressings are also effective and do not have the disadvantages of the cream. This preparation, however, is not available for general usage. For these reasons, we have devised a laminated dressing using the 11.2% cream and saline, which delivers an aqueous solution of mafenide acetate to the wound. The dressing has proved both effective and acceptable to patients, and is particularly valuable following the application of split-thickness skin grafts to burns and other chronic open wounds. The technique is described.

Pharmacology of sulfadiazine silver. Its attachment to burned human and rat skin and studies of gastrointestinal absorption and extension.

The attachment of Ag110-labeled sulfadiazine silver (AgSU) to the burn wound of humans and full and partial thickness scald burns of rats was studied over time. The duration of Ag adherence to burned skin and the absorption and organ distribution of ingested AgSU was studied. Peak attachment to human burns was 1% of the administered dose in 24 hours. Rat wounds showed greater attachment. Dissections of the wounds showed 81% to 98.7% of this attachment to be in the most superficial layers of cells and no silver was observed in organs of surface-treated animals. Duration of attachment after one application was until wound slough with percent attachment dropping from 5% to 1.7% over that time. Oral ingestion resulted in substantial silver deposition, particularly in liver and lungs. Clearance occurs in three weeks. The basic function of AgSU may be through the slow release of silver into the superficial wound environment.

Changes in anticoagulation in dogs assayed by three methods.

As a preliminary to a membrane oxygenator study, a study was made of clotting indices in dogs and their intercorrelation and relationship to human data. The most useful criterion for monitoring coagulation in experimental extracorporeal systems was sought. Linear regression and correlation analysis indicated that activated partial thromboplastin time (APTT) predicted whole blood clotting time with a correlation of 0.77 (p less than 0.01). Changes in the APTT with time after heparinization were similar to those previously reported in man, making the animal model an acceptable one for use in developing extracorporeal systems such as the membrane oxygenator. When blood activated recalcification time (BART), APTT, and whole blood clotting time (WBCT) assays were compared on the basis of applicability to studies of extracorporeal support, the APTT and the BART assays proved superior to the WBCT assay due to their reduced variability and increased speed of determination. The variability of the BART assay was the lowest, and its sensitivity was the same as the APTT assay. The principal drawback to the BART assay was not experienced in this study; that is, its dependence on adequate platelet levels which are unpredictable in extracorporeal systems.

Studies of the pain produced by mafenide acetate preparations in burns.

In a double-blind triple cross-over clinical study, 37 patients were exposed to several formulations of mafenide acetate (Sulfamylon Cream) and their pain responses were recorded and converted to a semiquantitative pain index. The 11.2% concentration in cream was two to three times more painful than the 5% concentration. Hypertonicity and not the pH level appears to be the cause of the pain produced by the high (11.2%) concentration. The tonicity of the cream carrier and 11.2% mafenide acetate are 1,080 mOsm/kg and 1,100 mOsm/kg, respectively, for a total of 2,180 mOsm/kg. The carrier cream without glycerol and a 5% concentration of mafenide cream were much less painful than the 11.2% concentration of mafenide. Both afforded a great deal of relief to the patients who received the medications.