Paul Nathan

A laboratory method for selection of topical antimicrobial agents to treat infected burn wounds

Summary This report describes an in vitro method which predicts the antimicrobial effects of the drugs which are used for topical application in the treatment of infected burn wounds. Standard in vitro disc sensitivities are not available for this panel of drugs. The test incorporates an evaluation of the drug carriers, creams and ointments, which are not factors in standard disc or dilution sensitivity methods. Quantitative bacteriological data following treatment of infected burn wounds in children support the conclusion that the in vitro test correctly selects effective antimicrobial agents.

A New Model for Studying the Development of Human Hypertrophic Burn Scar Formation

Hypertrophic scar formation remains the major problem for severely burned patients who survive their injuries. This scarring can result in both cosmetic and functional deformities. One of the major problems in dealing with this complication is the lack of an adequate animal model with which to test various possible therapeutic modalities. We describe an animal model that uses human skin applied to the backs of nude mice to investigate the problem. Immunosuppression is not necessary in this model since the nude mouse lacks a thymus gland and is therefore not able to reject the skin. With this model we have been able to achieve contracture of meshed normal human skin grafts and hypertrophic scar formation in normal human skin that was burned a month after grafting to the mouse. We have also had success in grafting human hypertrophic scars, obtained from burn patients, to the mice. This model offers unique opportunities for investigation of the cause and treatment of burn scars in humans.

Control of experimental burn wound infections: comparative delivery of the antimicrobial agent (silver sulfadiazine) either from a cream base or from a solid synthetic dressing.

This report demonstrates prolonged effective release of silver sulfadiazine (AgSD) to experimental burns in rats from a solid dressing by mixtures of polyethylene glycol-400 and poly-2-hydroxyethyl methacrylate. The synthetic dressing, incorporating the antimicrobial drug, may be formed either directly on the burn wound or prepared as a preformed sheet and applied to the wound after it was contaminated with bacteria. The level of silver in the blood following treatment of the burn wound with topical AgSD (Silvadene, Marion Labs) is significantly less when the drug is presented in the dressing than when the drug is applied in a cream base; the concentration of the sulfadiazine moiety in the blood is similar for the two drug preparations. Improved survival of the burned and contaminated rats and reduced nursing care were observed in the burned animals when the synthetic dressing was used to deliver the drug relative to the results when the AgSD was applied in a cream base by standard procedures.

Prospective clinical study of Hydron, a synthetic dressing, in delivery of an antimicrobial drug to second-degree burns.

This clinical trial prospectively evaluates the potential beneficial effects of antimicrobial drug delivery from a synthetic dressing (Hydron-AgSD) formed on second-degree burn wounds. A paste composed of polyethylene glycol-400, poly 2-OH ethylmethacrylate, and silver sulfadiazine (AgSD 1%-3%) matured within one hour to form a solid dressing. In 27 patients, comparable areas of second-degree wounds on the same patient were selected at random for test and control (silver sulfadiazine 1% only) sites. The mean total time of the synthetic dressing application per patient was about nine days, and each dressing remained in place for nearly four days. During this interval the control sites required four dressings changes. In 17 tests for infections, the control areas were contaminated but no bacteria were detected under the synthetic dressing; in three tests, the controls had no bacteria, whereas the synthetic dressing did. Healing of burns was similar under both types of dressing. Benefits of Hydron treatment included increased patient comfort because of the reduced number of dressing changes and, in some cases, greater freedom from contaminating bacteria.

Accelerated Idioventricular Rhythm in Pregnancy: A Case Report:

A seventeen-year-old primigravida, without structural heart disease or ab normalities of serum chemistry, presented with complaints of palpitations dur ing the twenty-fourth week of gestation. Holter monitoring revealed long episodes of accelerated idioventricular rhythm. The authors are not aware of similar reports, but this entity may be more common than realized because of the relative infrequency of rhythm monitoring in this particular group.

The microclimate chamber: the effect of continuous topical administration of 96% oxygen and 75% relative humidity on the healing rate of experimental deep burns.

The healing rate of small experimental burns continuously treated topically with 96% O2 and 75% relative humidity was followed for 25 days. Serial image photographic magnifications (tenfold throughout) of the wounds enabled precise measurements of their size by means of a polar planimeter. Healing rate was expressed as decreased percentile of wound size on a given day compared to the initial area. The mean percentages of healing +/- SEM of the humidified O2 treated wounds on postburn days 6, 11, and 16 were 31.25 +/- 6.15, 82.09 +/- 3.52, and 98.29 +/- 1.46, respectively, and those for the control wounds were 7.08 +/- 2.20, 47.68 +/- 3.39, and 84.41 +/- 1.38, respectively. Analysis of variance revealed highly significant differences in the healing rate between O2-humidity-treated and control wounds (p less than 0.005). The results indicate that topical treatment with 96% O2 and 75% relative humidity improved healing of experimental burns in guinea pigs.

Evaluation of storage conditions for refrigerated rabbit skin

Abstract An evaluation of various refrigerated (4 °C) storage solutions and conditions was conducted using rabbit skin. Two in vitro methods to assay skin viability are presented: one which directly measures basal cell viability and one which assesses the skins ability to grow in culture following storage. The superiority of storage in nutrient medium supplemented with fetal bovine serum over conventional storage in saline is clearly demonstrated. Storage in nutrient medium with 10% fetal calf serum resulted in basal cell viabilities which were over 30% higher than viabilities of skin stored by conventional methods in saline. Skin stored in saline failed to grow in culture, while 100% of the cultures of skin stored in medium plus fetal calf serum grew. Although addition of fetal calf serum to the saline improved the basal cell viability, growth in culture occurred only when the skin was stored in a capped tube. Skin stored in medium without serum gave viability results which were not significantly different from the unstored control, but growth rates in culture did differ significantly from the control values. Our study shows that the viability of rabbit skin and its ability to grow in vitro are depressed when the tissue is maintained at 4 °C in saline or in petri dishes, and optimal when refrigerated in nutrient medium supplemented with FBS in a sealed tube.

A method for transplantation of the rat kidney.

Laboratory studies on transplantation of the kidney have previously been conducted in species such as the dog because of the availability of established surgical methods for anastomoses of blood vessels in larger animals. After the development in our laboratory of microsurgical procedures suitable for connection of blood vessels in the rabbit: it became possible to extend the method to homologous renal transplants in the rat. The substitution of the rat for larger animals has a number of advantages. (1) Long-term survival of isologous organ transplants can be studied in highly inbred strains of rats. This provides better genetic control of experimental material than can be achieved a t this time with larger animals. (2) It reduces the cost of both the experimental animals and the surgical procedures. (3) The transplant technique in the rat does not require the careful asepsis that is needed in surgery on the dog. (4) The space for housing is reduced by use of a small animal. The present report describes our method for transplantation of the rat kidney from one animal to another. The transplants were performed by direct anastomoses of the aorta and vena cava of the donor to the carotid artery and jugular vein of the recipient. The results of the operation are illustrated with histological sections of biopsies from both homologous and isologous transplants.

A Clinical Study of Antimicrobial Agents Delivered to Burn Wounds from a Drug-loaded Synthetic Dressing

This report is of an investigation of the release of antimicrobial agents from a solid barrier dressing when applied to second- and third-degree burn wounds. The synthetic dressings were formed by a mixture of polyethylene glycol-400 (PEG), poly-2-hydroxethyl methacrylate (PHEMA) and one of the test drugs: silver sulfadiazine (AgSD), gentamicin, silver nitrate, or nitrofurazone. The dressings were formed directly on the burn wounds of 33 patients from a paste prepared from a mixture of PEG-PHEMA and drug. These dressings remained in place for 3 days, covering 12 to 64 square inches of the wound. In six patients, the entire burn wounds were covered with the dressings in which the treated areas were each about 200 square inches. The use of drug-loaded synthetic dressings extended to cover major portions of the burn wounds reduced the work required for nursing care and lessened patient discomfort.

Drug-loaded synthetic dressings: effect on contraction, epithelialization, and collagen synthesis of deep second-degree experimental burns.

The effect of drug-loaded synthetic dressings on the contraction, epithelialization, and collagen synthesis of deep second-degree burns was followed for 21 days in 44 guinea pigs. Two symmetrical burns were inflicted on the back of each animal: the animals were then divided at random into the following test groups: Group 1 (n=10), a prefabricated, precut, pliable, and noncracking dressing designated as Dimac (DM), versus Dimac plus 2% silver sulfadiazine (DM +); Group 2 (n=10), Hydron loaded with 2% silver sulfadiazine (HAgS) one versus fine mesh gauze and 1% silver-sulfadiazine cream (GAgS); Group 3 (n=12), Hydron (Hyd) versus fine mesh gauze (G); Group 4 (n=4), fine mesh gauze versus Telfa (Tel); Group 5 (n=6), Telfa versus Telfa; Group 6 (n=2), gauze versus gauze. Epithelialization and contraction rates were measured at dressing changes on postburn days 6, 12, 18, and 21, with a computerized sonic digitizer. Collagen biosynthesis was measured from the wound scar on PBD 21 and expressed as relative collagen biosynthesis. Contraction on PBDs 18 to 21 was significantly lower (p<0.05) in the DM and DM+ treated burns. Epithelialization of the DM and DM+ treated groups on PBD 21 was significantly (p<0.05) higher than in the Hyd, HAgS, GAgS, and Tel treated burns, and did not differ from the G treated wounds. The relative collagen biosynthesis method was inapplicable to this burn wound model.