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Benefits of AgSD plus quinolones
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Murine model for studies of neuromuscular dysfunction A murine burn model was tested to determine whether it could simulate the neuromuscular (NM) dysfunction seen in burned patients. Metabolic rates, immune response to dinitrofluorobenzene (DNFB), maximal tension developed by the gastrocnemius muscle and the response of its NM junction to d-tubocurarine (dTc) were assessed in control mice and mice given burns covering 20 per cent, 30 per cent and 50 per cent of the total body surface area. By 21 days after injury all the burn groups showed-elevated metabolic rates and immunosuppression to the inflammatory DNFB. NM dysfunction was observed in the animals with 30 and 50 per cent burns. A three-fold increase in the effective dose (ED,,) values of dTc was only seen in the 50 per cent bum group. No NM junctional changes were seen in the 20 per cent bum group. As all these findings are found in patients with the same extent of bums, the mouse bum model can be used to study the dysfunction mechanisms in more detail. Tomera J. F., Martyn J. and Hoaglin D. C. (1988) Neuromuscular dysfunction in burns and its relationship to burn size, hypermetabolism and immunosuppression. 1. Trauma 28, (lo), 14991504. Stimulated granulocyte production and infection Mice with a 15 per cent body surface area bum wound that had also been seeded with 10’ Ps. aeruginosa organisms showed an improved mean survival time following subcutaneous administration of recombinant human granulocyte colony-stimulating factor. The administration of this factor also augmented the myelopoietic response as shown by significantly increased white blood cell counts, neutrophil counts, splenic weight, femoral marrow cellularity and femoral marrow granulocyte-macrophage colony forming cell count. Mooney D. P., Gamelli R. L., O’Reilly M. et al. (1988) Recombinant human granulocyte colony-stimulating factor and Pseudomonas bum wound sepsis. Arch. Surg. 123, (II), 1353-1357. Benefits of AgSD plus quinolones Studies were made of the combined use of silver sulphadiazine and quinolones on the development of resistant strains of Ps. aerugitwsa.In vitro serial subcultures through subinhibitory concentrations of norfloxacin and pefloxacin gave MIC increases of 40 times, whereas when the cultures were passed through a combina-
Burns (1989) Vol. 15/No. z
tion of AgSD and these quinolones the MIC of the quinolones increased only TO-fold. When burned mice infected with either AgSD-sensitive or -resistant Ps. aerhgimsa strains were treated in vivo with a topical cream containing AgSD and the quinolones, the mortality was much lower than that of AgSD alone or quinolones alone; results which suggest that the combination of the drugs discouraged the emergence of resistant mutants. Modak S. M., Sampath L. and Fox C. L. (1988) Combined topical use of silver sulfadiazine and antibiotics as a possible solution to bacterial resistance in bum wounds. 1. Bum Care R&&l. 9, (4), 359-363.
Cachectin/TNF and infection Body compositional changes and in vivo hepatic levels of pretranslational messengers for cachectin were measured in the following groups of rats: freely fed; pair fed; with a 30 per cent TBSA burn; a 30 per cent bum with pseudomonas infection; and a 30 per cent bum with infection and recombinant cachectin. Compared with controls or animals only burned, burned and infected rats had a 100 per cent increase in hepatic cachectin messenger RNA content, loss of carcass protein and showed muscle loss with sparing of liver mass. Marano M. A., Moldawer L. L., Fong Y. et al. (1988) CachectinITNF production in experimental bums and pseudomonas infection. Arch. Surg., 123, (111 1383-1388.
Superoxides and lung injury Since smoke inhalation injury and ARDS have many features in common, studies were carried out in an ARDS model to assess superoxide production by circulating and bronchoalveolar lavage (BAL) polymorphonuclear leucocytes. Both these groups of cells were found to be primed for non-selective increased superoxide production. The BAL cells were also partially primed to release superoxide on adherence and had a depressed superoxide response to a phagocytic stimulus. Such changes may induce pulmonary injury and increase the susceptibility to pulmonary infection. Holman R. G. and Maier R. V. (1988) Superoxide production by neutrophils in a model of adult respiratory distress syndrome. Arch. Surg, 123, (IL), 1491-1495.
Murine model for studies of neuromuscular dysfunction A murine burn model was tested to determine whether it could simulate the neuromuscular (NM) dysfunction seen in burned patients. Metabolic rates, immune response to dinitrofluorobenzene (DNFB), maximal tension developed by the gastrocnemius muscle and the response of its NM junction to d-tubocurarine (dTc) were assessed in control mice and mice given burns covering 20 per cent, 30 per cent and 50 per cent of the total body surface area. By 21 days after injury all the burn groups showed-elevated metabolic rates and immunosuppression to the inflammatory DNFB. NM dysfunction was observed in the animals with 30 and 50 per cent burns. A three-fold increase in the effective dose (ED,,) values of dTc was only seen in the 50 per cent bum group. No NM junctional changes were seen in the 20 per cent bum group. As all these findings are found in patients with the same extent of bums, the mouse bum model can be used to study the dysfunction mechanisms in more detail. Tomera J. F., Martyn J. and Hoaglin D. C. (1988) Neuromuscular dysfunction in burns and its relationship to burn size, hypermetabolism and immunosuppression. 1. Trauma 28, (lo), 14991504. Stimulated granulocyte production and infection Mice with a 15 per cent body surface area bum wound that had also been seeded with 10’ Ps. aeruginosa organisms showed an improved mean survival time following subcutaneous administration of recombinant human granulocyte colony-stimulating factor. The administration of this factor also augmented the myelopoietic response as shown by significantly increased white blood cell counts, neutrophil counts, splenic weight, femoral marrow cellularity and femoral marrow granulocyte-macrophage colony forming cell count. Mooney D. P., Gamelli R. L., O’Reilly M. et al. (1988) Recombinant human granulocyte colony-stimulating factor and Pseudomonas bum wound sepsis. Arch. Surg. 123, (II), 1353-1357. Benefits of AgSD plus quinolones Studies were made of the combined use of silver sulphadiazine and quinolones on the development of resistant strains of Ps. aerugitwsa.In vitro serial subcultures through subinhibitory concentrations of norfloxacin and pefloxacin gave MIC increases of 40 times, whereas when the cultures were passed through a combina-
Burns (1989) Vol. 15/No. z
tion of AgSD and these quinolones the MIC of the quinolones increased only TO-fold. When burned mice infected with either AgSD-sensitive or -resistant Ps. aerhgimsa strains were treated in vivo with a topical cream containing AgSD and the quinolones, the mortality was much lower than that of AgSD alone or quinolones alone; results which suggest that the combination of the drugs discouraged the emergence of resistant mutants. Modak S. M., Sampath L. and Fox C. L. (1988) Combined topical use of silver sulfadiazine and antibiotics as a possible solution to bacterial resistance in bum wounds. 1. Bum Care R&&l. 9, (4), 359-363.
Cachectin/TNF and infection Body compositional changes and in vivo hepatic levels of pretranslational messengers for cachectin were measured in the following groups of rats: freely fed; pair fed; with a 30 per cent TBSA burn; a 30 per cent bum with pseudomonas infection; and a 30 per cent bum with infection and recombinant cachectin. Compared with controls or animals only burned, burned and infected rats had a 100 per cent increase in hepatic cachectin messenger RNA content, loss of carcass protein and showed muscle loss with sparing of liver mass. Marano M. A., Moldawer L. L., Fong Y. et al. (1988) CachectinITNF production in experimental bums and pseudomonas infection. Arch. Surg., 123, (111 1383-1388.
Superoxides and lung injury Since smoke inhalation injury and ARDS have many features in common, studies were carried out in an ARDS model to assess superoxide production by circulating and bronchoalveolar lavage (BAL) polymorphonuclear leucocytes. Both these groups of cells were found to be primed for non-selective increased superoxide production. The BAL cells were also partially primed to release superoxide on adherence and had a depressed superoxide response to a phagocytic stimulus. Such changes may induce pulmonary injury and increase the susceptibility to pulmonary infection. Holman R. G. and Maier R. V. (1988) Superoxide production by neutrophils in a model of adult respiratory distress syndrome. Arch. Surg, 123, (IL), 1491-1495.