thymus metabolism and cortisol levels

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Abstracts 287 Leucopenia and silver sulphadiazine Leucopenia with a mean white blood cell count of 2680/mm3 has been observed in 9 oatients with burns early in the course of topical treatment with silver sulphadiazine. All patients showed absolute neutro- penia with a concomitant increase in immature bond forms in the peripheral blood smear. The leucocyte counts returned to within normal limits within 2 to 3 days of stopping therapy with silver sulphadiazine in 4 patients, and also did so in 5 patients in whom thera- py with silver sulphadiazine was continued. Leucopenia secondary to therapy with silver sulphadiazine appears to be innocuous and to correct itself spontaneously. Jarrett F., Ellerbe S. and Demling R. (1978) Acute leukopenia during topical burn therapy with silver sulfadiazine. Am. J. Surg. 135, 818. Cardiac output and circulatory dynamics Pulmonary artery catheterization was performed in 39 critically burned patients (EAB, 15-94 per cent, mean, 61 per cent). Haemodynamic changes induced by burning and its therapy were measured. Pulmonary wedge pressure was found to be a more reliable indicator of circulating volume, whereas central venous pressure was often misleading. Measurements of both pulmonary haemodynamics and cardiac output were necessary to manage patients requiring high levels of pulmonary end expiratory pressure (PEEP). These measurements made it possible to define optimum PEEP levels which provided maximum oxygen de- livery to the tissues. Depressed myocardial function was seen soon after burning and administration of dopamine at this time increased left ventricular stroke work index with minimal changes in filling pressures. Catheter-related complications were minima1 when the catheters were used for periods of 3 days or less. Aikawa N., Jeevendra-Martin J. A. and Burke J. F. (1978) Pulmonary artery catheterization and thermo- dilution cardiac output determination in the manage- ment of critically burned patients. Am. .I. Surg. 135, 811. Immunosuppressive sera The sera from 51 burned patients with a wide range of severity of injuries were tested for immunosuppressive activity. A variable but significant percentage of the sera suppressed the response of normal human peri- pheral blood lymphocytes to phytohaemagglutinin. The occurrence of immunosuppressive activity paralleled the severity of the burn. All severely burned patients (severity index >40) but only 20 of 30 patients with indices 10 to 39.9 and 3 of 11 patients with indices between 0 and 9.9 developed suppressive serum. The differences between these groups were significant at the level of PcO.05. In all 19 patients who became septic, immunosuppressive serum activity immediately preceded or coincided with the septic episode. In contrast to the effect on lymphocytes, the sera from the burned patients stimulated the proliferation of fibroblasts. Immunosuppressive ac- tivity did not correlate with serum cortisol levels, blood transfusion, protein-calorie malnutrition or anaesthesia. Suppressive sera were not cytotoxic. Most of the active serum factors were contained in a poly- peptide fraction with a molecular weight of less than 10 000 daltons. Constantian M. B. (1978) Association of sepsis with an immunosuppressive polypeptide in serum of burn patients. Ann. Surg. 188, 209. Ribonuclease activity The activity of alkaline ribonuclease and the level of urate in the serum and urine has been measured in burned patients. Ribonuclease activity was elevated in all burned patients, the degree of elevation being related to both the area of the burn and to a predictive index of mortality. Increased serum ribonuclease activity was accompanied by an increased urinary output of the enzyme. There was also a significant correlation between the serum urea level and ribo- nuclease activity during the first week after burning. This correlation was probably the result of increased protein catabolism and renal dysfunction. Such a correlation disappeared after this time with the increased ribonuclease activity more likely due to tissue repair. Serum urate concentrations were decreased in all burned patients, and when expressed in terms of the expected normal (or value on admission to hospital) were very strongly correlated with the predictive index of burn mortality. In severely burned patients the decrease in serum urate was accompanied by in- creased urine urate output, probably indicating a change in the renal handling of urate after burning. Coombes E. J., Shakespeare P. G. and Batstone G. F. (1978) Observations on serum and urine alkaline ribonuclease activity and urate after burn injury in man. C/in. Chim. Acta 86, 279. Pseudomonas vaccine trial In a controlled clinical trial of a polyvalent pseudo- monas vaccine in burned patients infected with Pseudomonas aeruginosa all 18 vaccinated patients survived whereas 8 of 20 unvaccinated patients died. Jones R. J., Roe E. A. and Gupta 3. L. (1978) Low mortality in burned patients in a pseudomonas vac- cine trial. Lancer 2, 401. ANIMAL STUDIES Thymus metabolism and cortisol levels Burns covering more than 15-30 per cent of the body surface are associated with both an acquired immuno- logical deficiency in the cell-mediated, thymus-regu- lated immunity and a significant increase in the gluco- corticoid levels. Since most thymus lymphocytes undergoing maturation are sensitive to cortisol, studies were carried out to measure the synthesis of nucleic acid and proteins in the thymus in relation to raised cortisol levels during the first week following a

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Page 1: Thymus metabolism and cortisol levels

Abstracts 287

Leucopenia and silver sulphadiazine Leucopenia with a mean white blood cell count of 2680/mm3 has been observed in 9 oatients with burns early in the course of topical treatment with silver sulphadiazine. All patients showed absolute neutro- penia with a concomitant increase in immature bond forms in the peripheral blood smear. The leucocyte counts returned to within normal limits within 2 to 3 days of stopping therapy with silver sulphadiazine in 4 patients, and also did so in 5 patients in whom thera- py with silver sulphadiazine was continued. Leucopenia secondary to therapy with silver sulphadiazine appears to be innocuous and to correct itself spontaneously.

Jarrett F., Ellerbe S. and Demling R. (1978) Acute leukopenia during topical burn therapy with silver sulfadiazine. Am. J. Surg. 135, 818.

Cardiac output and circulatory dynamics Pulmonary artery catheterization was performed in 39 critically burned patients (EAB, 15-94 per cent, mean, 61 per cent). Haemodynamic changes induced by burning and its therapy were measured. Pulmonary wedge pressure was found to be a more reliable indicator of circulating volume, whereas central venous pressure was often misleading. Measurements of both pulmonary haemodynamics and cardiac output were necessary to manage patients requiring high levels of pulmonary end expiratory pressure (PEEP). These measurements made it possible to define optimum PEEP levels which provided maximum oxygen de- livery to the tissues. Depressed myocardial function was seen soon after burning and administration of dopamine at this time increased left ventricular stroke work index with minimal changes in filling pressures. Catheter-related complications were minima1 when the catheters were used for periods of 3 days or less.

Aikawa N., Jeevendra-Martin J. A. and Burke J. F. (1978) Pulmonary artery catheterization and thermo- dilution cardiac output determination in the manage- ment of critically burned patients. Am. .I. Surg. 135, 811.

Immunosuppressive sera The sera from 51 burned patients with a wide range of severity of injuries were tested for immunosuppressive activity. A variable but significant percentage of the sera suppressed the response of normal human peri- pheral blood lymphocytes to phytohaemagglutinin. The occurrence of immunosuppressive activity paralleled the severity of the burn. All severely burned patients (severity index >40) but only 20 of 30 patients with indices 10 to 39.9 and 3 of 11 patients with indices between 0 and 9.9 developed suppressive serum. The differences between these groups were significant at the level of PcO.05. In all 19 patients who became septic, immunosuppressive serum activity immediately preceded or coincided with the septic episode. In contrast to the effect on lymphocytes, the sera from the burned patients stimulated the proliferation of fibroblasts. Immunosuppressive ac-

tivity did not correlate with serum cortisol levels, blood transfusion, protein-calorie malnutrition or anaesthesia. Suppressive sera were not cytotoxic. Most of the active serum factors were contained in a poly- peptide fraction with a molecular weight of less than 10 000 daltons.

Constantian M. B. (1978) Association of sepsis with an immunosuppressive polypeptide in serum of burn patients. Ann. Surg. 188, 209.

Ribonuclease activity The activity of alkaline ribonuclease and the level of urate in the serum and urine has been measured in burned patients. Ribonuclease activity was elevated in all burned patients, the degree of elevation being related to both the area of the burn and to a predictive index of mortality. Increased serum ribonuclease activity was accompanied by an increased urinary output of the enzyme. There was also a significant correlation between the serum urea level and ribo- nuclease activity during the first week after burning. This correlation was probably the result of increased protein catabolism and renal dysfunction. Such a correlation disappeared after this time with the increased ribonuclease activity more likely due to tissue repair.

Serum urate concentrations were decreased in all burned patients, and when expressed in terms of the expected normal (or value on admission to hospital) were very strongly correlated with the predictive index of burn mortality. In severely burned patients the decrease in serum urate was accompanied by in- creased urine urate output, probably indicating a change in the renal handling of urate after burning.

Coombes E. J., Shakespeare P. G. and Batstone G. F. (1978) Observations on serum and urine alkaline ribonuclease activity and urate after burn injury in man. C/in. Chim. Acta 86, 279.

Pseudomonas vaccine trial In a controlled clinical trial of a polyvalent pseudo- monas vaccine in burned patients infected with Pseudomonas aeruginosa all 18 vaccinated patients survived whereas 8 of 20 unvaccinated patients died.

Jones R. J., Roe E. A. and Gupta 3. L. (1978) Low mortality in burned patients in a pseudomonas vac- cine trial. Lancer 2, 401.

ANIMAL STUDIES Thymus metabolism and cortisol levels Burns covering more than 15-30 per cent of the body surface are associated with both an acquired immuno- logical deficiency in the cell-mediated, thymus-regu- lated immunity and a significant increase in the gluco- corticoid levels. Since most thymus lymphocytes undergoing maturation are sensitive to cortisol, studies were carried out to measure the synthesis of nucleic acid and proteins in the thymus in relation to raised cortisol levels during the first week following a

Page 2: Thymus metabolism and cortisol levels

288 Burns Vol. ~/NO. 3

30 per cent, full-thickness skin loss scald in young guinea-pigs. At various times after burning suspensions of thymus cells from both burned and control animals were incubated in vitro with %thymidine, %r-uridine or %aminoacids to assess the synthesis of DNA, RNA and protein respectively. Parallel measurements of 24 h free urinary cortisol levels were performed by radioimmunoassay. The observed decreases to 64 and 83 per cent of the control values in DNA and RNA synthesis respectively, at 6 days after burning, were independent of the changes in the uptake of precursor. The decreased nucleic acid synthesis was associated with 24 h free urinary cortisol levels which were near twice the control values and cortisol levels in the

thymus which were three times the control values. These results suggested that the changes in thymus metabolism associated with elevated cortisol levels could contribute to suppression of T lymphocyte production or maturation and result in a relative immunodeficient state.

Sajdel-Sulkowska E., Kumar A., Clairmont G. et al. (1978) Elevated cortisol levels and changes in thymus metabolism in burn trauma. Burns 5, 136.

Abstracts compiled by J. W. L. Davies, DSc, MRC Industrial Injuries and Burns Unit, Birmingham Accident Hospital, Bath Row, Birmingham, B15 INA.

Addendum Francis S. Knox, III, Thomas L. Wachtel and Stanley C. Knapp, the authors of ‘How to measure the burn-preventive capability of non-flammable textiles: a comparison of the USAARL porcine bioassay technique with mathematical models’, which appeared in Burns Vol. ~/NO. 1, wish to point out that the following Acknowledgements should have appeared with the article:

The authors wish to thank the able staff of the US Army Aeromedical Research Laboratory for their help in conducting these experiments and Ransom Nockton, Daniel Reneau and Chester Ellis for programming support. Funds for this work were provided under contract DABTO 1-75-C-0257 and DAMD 17-77- C-7004 with the US Army Aeromedical Research Laboratory and the US Army Medical Research and Development Command respectively.