406
binted
Bums (1990) 16, (6), 40&413
in Great Britain
Superoxide dismutase prevents lipid peroxidation in burned patients P. D. Thomson, G. 0. Till, J. 0. Woolliscroft, D. J. Smith and J. K. Prasad University of Michigan Medical Center, Ann Arbor, Michigan, USA
Animul mod& and humanstudieshave shmn fhaf wnjugafeddienc5 rise infkp&maa&rfknnalinju~. %sedienesmaysemeasamar~of
oxygenra&aCmediatedtissueinjwy. Twelvebum patientswerz tund&&d fo reu&e tk antioxidant enzyme polyethyleneglyrwl-conjugat~ superox~&dismut% (PEGSOD). Patimts rem&d eifkr 500 or 1000 unifs per kilogram of PEG-SOD infravemusly z&in 6 h of injury. P&mm samples were wllecfed and conjugateddiene &meLwere compatzd fodieneleoe&ofbunrpntinltsMttreatedandfodienelmelsfnrmrunmnl volunteers. Conjugafed a%ne levet!swere itumsed in bwn @ients. PEG-SOD in either dose in&ally decreawi conjugated diene levels in fk plamaofbothtreatmentgrmcps.By72h,tkdimelewlsinrrcwcdintk 500 unit&group, but remained at near controll&e12in fk MOOunit/k group forup to 200 h a@ injury. These data west that PEG-SOD is cap&& of preventing cmjqgafed diem formed astk result d oqtgen radical production.It appears that 1000 units/kg is more e&five fhan 500 units/h in preuenfing conjugateddienef&nation.
Introduction Inflammatory responses initiated either by trauma (Recknagel and Ghoshal, 1966; Hiramatsu and Izawa, 1984) or by endotoxin (Demliig et al., 1988) initiate a cascade of events which results in the generation of oxygenderived free radicals subsequently causing the peroxidation of membrane phospholipids. The oxidation of polyunsaturated fatty acids from membrane phospholipids may produce additional free radicals which in turn stimulate further lipid peroxidation and tissue injury. In this self-generating chain reaction, free radical attack on double bonds of methylene groups creates random cross-linking of lipid degradation products. These reactive byproducts, conjugated dienes, may be detected in the plasma of burn patients (Woolliscroft et al., 1990) as increases in ultraviolet absorption. These conjugated dienes therefore may be used to indicate free radical-mediated tissue injury (Till et al., 1985; Romaschin et al., 1987; Demling et al., 1988). Extracts from burn plasma yield conjugated dienes which, although non-specific and transient, may provide an indication of the magnitude of the initial trauma or of the ensuing leucocyte-mediated inflammatory response (Till et al., 1985). Interventions designed to interrupt this cascade of events have included antihistamines, oxygen radical scavengers and metal chelators which have been reviewed
elsewhere
0 1990 Butterworth-Heinemann 03054179/90/060406-03
(Till et al., 1990). It has been Ltd
previously shown in animal models that the antioxidant enzyme superoxide dismutase provides protection from tissue injury mediated by superoxide anion (Johnson and Ward, 1981; McCormick et al., 1981). The present study, a phase I clinical trial, investigated the effect of the stabilized antioxidant enzyme, polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), on plasma-conjugated dienes in thermally injured human patients.
Materials and methods Informed consent was obtained from 12 burn patients admitted to this Bum Centre. These burn patients ranged in age from 20 years to 73 years and the extent of burn ranged from 14 per cent to 45 per cent total body surface area (Tub&I). Immediately after admission and within 6 h postburn, these patients were given a single, intravenous dose of PEG-SOD (Enzon, Inc., South Plainfield, NJ, USA). The first six patients received 5OOunits PEG-SOD/kg of body weight and the other six patients received 1000 units/kg. Blood samples were collected prior to PEG-SOD admiistration and every 6 h initially, every 12 h for 2 days and then every 24 h thereafter for up to 200 h postbum. These blood samples were collected in tubes containing 10 ITIMethylene diamine tetra-acetic acid. Samples were kept on ice and plasma was immediately separated by centrifugation at 4’C and 3ooO rev./min. Plasma was then frozen at - 70°C until assayed. Products of lipid peroxidation (conjugated dienes) were extracted from these plasma samples in chloroformmethanol, dried under nitrogen and resuspended in heptane for absorption measurements using a previously described method (Till et al., 1985; Ward et al., 1985). These extracts were subjected to spectrophotometric analysis at 233 nm. Absorbance data for samples collected from each time 72-120 and 120-200 h) were period (6-24,2448,48-72, compared between treatment groups and compared to plasma samples from patients who were burned but not treated with PEG-SOD. There were 24 paired samples analysed for each time period and each treatment group. Statistical analysis (Godfrey, 1985) was pexformed using
analysis of variance (ANOVA) and data were expressed as mean f standard error of the mean. Statistical significance was defined as P< 0.05 by ANOVA.
Thomson et al.: SOD in
burned patients
407
Table I.
Demographics (mean f standard error) of cotitrol burn patients and bum patients treated with a single intravenous dose of either 500 or 1000 units of PEG-SOD per kilogram of body
?a&
IL Conjugated di ene levels of bum patients with and without treatment with intravenous PEG-SOD Conjugated diene levels (absorbance at 233nmA s.e.m.‘)
weight PEG-SOD dose
PEG-SOD treated
Contror
500 units/kg’
7000 units/kg*
Mean Range
42.7h5.1 (28-60)
42.2 f 7.3 (20-58)
47.8 f 7.9 (26-73)
%TBSA burn Mean Range
40.5f 9.5 (25-79)
24.0 f 4.2 (14-43)
28.2 f 3.9 (17-45)
Age (W
TBSA, ‘n=6.
total body surface
Time after burn injuty
500 units/kg
1000 units/kg
Pre PEG-SOD Post PEG-SOD 24h 48h 72h 120h 200 h
0.61 f 0.07
0.88 f 0.35
0.62zkO.12 0.59 f 0.08’ 1.30 f 0.37 0.97 f 0.25 1.11 zto.30
0.52 f 0.13 0.55*0.13 0.39 f 0.01. 0.61 f 0.15” 0.48 f 0.08
ND, no data. *P < 0.05 compared
to control
Control
ND 1.56kO.02 1.39k 0.31 1.38*0.19 ND
area.
Results Burn patients treated with 500 units of PEG-SOD/kg showed an initial decline in plasma-conjugated dienes, but diene levels returned to control levels by 72 h postbum (TubleII). Those patients who received IO00 units PEGSOD/kg showed significantly lowered levels of plasma conjugated dienes up to 120 h postbum when compared to controls. In this group of patients, plasma diene levels remained lowered up to 200 h when compared to the group receiving 500 units/kg. A group of six non-age-matched normal volunteers showed mean plasma levels of conjugated dienes of 0.48 absorbance units. It was noted that pre PEGSOD levels of conjugated dienes were higher than normal in both bum treatment groups, and were higher in the 1000 unit/kg group than either the 500 unit/kg or control group. Treatment with 1000 unit/kg almost completely prevented the appearance of lipid peroxidation products (conjugated dienes) in the plasma of burn patients within 24 h of treatment.
Discussion These data suggest that intravenous administration of the antioxidant enzyme PEG-SOD decreases the plasma levels of lipid peroxidation products in burn patients. These data also suggest that, when administered immediately postbum, 1000 unit/kg of PEG-SOD is more effective in reducing plasma levels of conjugated dienes than is 500 unit/kg. The rise in lipid peroxides of untreated control bum patients in this study is consistent with the findings of other investigators who have shown lipid peroxide levels to rise consistently in the immediate postbum period. Although the untreated control patients had a larger mean percentage bum, ANOVA showed that the group was not significantly different from the two treatment groups. Conjugated diene levels in the untreated burns were similar to those seen in the smaller mean bum size of the 500 unit/kg group when treatment appeared to fail after 72 h. Products of lipid peroxidation are somewhat variable in nature and appear to be higher in larger bums, but do not appear to correlate with mortality probability (Gosling et al., 1988). In this patient population it was observed that the larger burns did have mean levels of dienes similar to mean levels of dienes observed in the smaller bums, however, some larger bums had single absorbance readings in excess of 4.0. These dif-
levels.
ferences in diene levels may be explained by the transient nature of the dienes, sample size or sample time. However, the data support the conclusion that PEG-SOD prevents oxygen radical-mediated conjugated diene formation. Although Demling et al. (1988) have reported that after endotoxin challenge conjugated dienes are cleared rapidly from the circulation, it appeared in these bum patients that conjugated dienes persisted for up to 8 days as shown previously by Hiramatsu and Jzawa (1984). It may be proposed that the dienes measured in this study were not the initial membrane phospholipid peroxidation products generated as the direct result of the bum injury. but were those produced by leucocytes involved in the ensuing inflammatory response (Till et al., 1983; Moore et al., 1986). There is published evidence to suggest that removal or prevention of peroxidation products lessens the inflammatory response by reducing chemoattractant lipids in injured tissue (Petrone et al., 1980). The prevention of lipid peroxidation products by elimination of superoxide anion has been shown in this study; however, it is yet to be demonstrated that this treatment has clinical relevance. Further investigation is required to determine clinical efficacy of such treatments.
References Dernling R. H., Lalonde C., Ryan P. et al. (1988)
Endotoxemia
produces an increase in arterial but not venous lipid peroxides in sheep.]. Appl.Physiol, 64, 592. Godfrey K. (1985) StaMics in practice comparing the means of several groups. N. Engl. J Med. 313, Gosling
P., Sukliffe
A.
1450.
J.,Cooper M. A. C. S. et
al. (1988)
Burnand
trauma associated proteinuria: the role of lipid peroxidation, renin and myoglobin. Ann. Clin.Biuch. 25,53. Hiramatsu M. and Izawa Y. (1984) Serum lipid peroxide levels of patients suffering thermal injury. Bums 11,111. Johnson K. J. and Ward P. A. (1981) Role of oxygen metabolites in immune complex injury of lung. _I.Immun01. 126‘2365.
McCormick J. R., Harkin M. M., Johnson, K. J. et al. (1981)
Sup-
pression by superoxide dismutase of immune-complex-induced puhnonary alveolitis and dermal infknmation. Am. J P&d 102,
55.
Moore F. D., Davis C., Rodrick M. et al. (1986) Neutrophil activation in thermal injury as assessed by increased expression of complement receptors. New Engl. J A/lad. 314,948.
Bums (1990) Vol. 16/No.
408
Petrone W. F., English D. K., Wong K. et al. (1980) Free radicals and inflammation: the superoxide dependent activation of a neutrophil chemotactic factor in plasma. Proc. Nutl. Aced. So. USA 77, 1159. Recknagel R. 0. and Ghoshal A. K. (1966) Lipoperoxidation as a vector in carbon tetrachloride hepatotoxicity. Lab. Inmt. 15, 132. Romaschin A. D., Rebeyka I., Wilson G. J. et al. (1987) Conjugated dienes in ischemic and reperfused myocardium: an in vivo chemical signature of oxygen free radical mediated injury. J. Mol. Cell. CardioJ. 19, 289. Till G. O., Beauchamp C., Menapace D. et al. (1983) Oxygen radical dependent lung damage following thermal injury of rat skin. J. Trauma 23,269. Till G. O., Hatherill J. R., Tourtellotte W. W. et al. (1985) Lipid peroxidation and acute lung injury after thermal trauma to skin. Am. J. Pafhol. 119, 376.
Till G. O., Friedl H. P. and Ward P. A. (1990) Phagocytic cellmediated injury: relationship to ischemic injury. In: Zelenock G. B. (ed.), Clinical lschetnic Syndromm Mechanism and Consequolces of Time Injury. St Louis, Mosby, pp. 327-345. Ward P. A., Till G. O., Hatherill J. R. et al. (1985) Systemic complement activation, lung injury and products of lipid peroxidation. J. Chn. haed. 76, 517. Woolliscroft J. O., Prasad J. K., Thomson P. D. et al. (1990) Metabolic alterations in burn patients: detection of adenosine triphosphate degradation products and lipid peroxides. Bums 16, 92.
Paper accepted
15 June 1990.
Correspondenceshould be uddd to: Dr P. D. Thomsom, University of Michigan Bum Center, lC435/0033 University of Michigan Hospital, Ann Arbor, MI 48109, USA.
BritishAssociation of PlasticSurgeons Advanced Courses in PlasticSurgery The sixth meeting of the above course will be held on Trauma of the Upper Limbs/Peripheral Nerve Surgery at Mount Vernon Hospital, Northwood on 819 Fetiruary 1991. The seventh meeting will be held on Lower Limb Trauma/Lymphoedema/Leg Ulcers in Bristol on 8/9 April 1991. The eighth meeting of the above course will be held on Burns in Mar&ester on 17/18 July 1991. The courses are aimed at consultants and trainees in plastic surgery but readers of Bum are invited to attend. The fee will be E200 which includes one night’s accommodation and all meals. Further details and an application form: British Association of Plastic Surgeons, The Royal College of Surgeons of England, 3543 Liicoln’s Inn Fields, London WCZA 3PN. Tel: 071-831-516112;
6
Fax 071-8314041.
3rd Congress on Bum Treatment Kosice, Czechoslovakia 13-14 June 1991 The main topics of the meeting will be: 0 Prevention ??Reconstruction and Rehabilitation of Burns 0 Inununology 0 Disaster Planning. The meeting will coincide with the 20th anniversary of the Burn Centre in Kosice. For information please contact: JaroslavBlaha, M.D., President of Congress, Centre for Bum Treatment, and Reconstructive Surgery, ZUNZ Kosice-Saca 04453, Czechoslovakia.
binted
Bums (1990) 16, (6), 40&413
in Great Britain
Superoxide dismutase prevents lipid peroxidation in burned patients P. D. Thomson, G. 0. Till, J. 0. Woolliscroft, D. J. Smith and J. K. Prasad University of Michigan Medical Center, Ann Arbor, Michigan, USA
Animul mod& and humanstudieshave shmn fhaf wnjugafeddienc5 rise infkp&maa&rfknnalinju~. %sedienesmaysemeasamar~of
oxygenra&aCmediatedtissueinjwy. Twelvebum patientswerz tund&&d fo reu&e tk antioxidant enzyme polyethyleneglyrwl-conjugat~ superox~&dismut% (PEGSOD). Patimts rem&d eifkr 500 or 1000 unifs per kilogram of PEG-SOD infravemusly z&in 6 h of injury. P&mm samples were wllecfed and conjugateddiene &meLwere compatzd fodieneleoe&ofbunrpntinltsMttreatedandfodienelmelsfnrmrunmnl volunteers. Conjugafed a%ne levet!swere itumsed in bwn @ients. PEG-SOD in either dose in&ally decreawi conjugated diene levels in fk plamaofbothtreatmentgrmcps.By72h,tkdimelewlsinrrcwcdintk 500 unit&group, but remained at near controll&e12in fk MOOunit/k group forup to 200 h a@ injury. These data west that PEG-SOD is cap&& of preventing cmjqgafed diem formed astk result d oqtgen radical production.It appears that 1000 units/kg is more e&five fhan 500 units/h in preuenfing conjugateddienef&nation.
Introduction Inflammatory responses initiated either by trauma (Recknagel and Ghoshal, 1966; Hiramatsu and Izawa, 1984) or by endotoxin (Demliig et al., 1988) initiate a cascade of events which results in the generation of oxygenderived free radicals subsequently causing the peroxidation of membrane phospholipids. The oxidation of polyunsaturated fatty acids from membrane phospholipids may produce additional free radicals which in turn stimulate further lipid peroxidation and tissue injury. In this self-generating chain reaction, free radical attack on double bonds of methylene groups creates random cross-linking of lipid degradation products. These reactive byproducts, conjugated dienes, may be detected in the plasma of burn patients (Woolliscroft et al., 1990) as increases in ultraviolet absorption. These conjugated dienes therefore may be used to indicate free radical-mediated tissue injury (Till et al., 1985; Romaschin et al., 1987; Demling et al., 1988). Extracts from burn plasma yield conjugated dienes which, although non-specific and transient, may provide an indication of the magnitude of the initial trauma or of the ensuing leucocyte-mediated inflammatory response (Till et al., 1985). Interventions designed to interrupt this cascade of events have included antihistamines, oxygen radical scavengers and metal chelators which have been reviewed
elsewhere
0 1990 Butterworth-Heinemann 03054179/90/060406-03
(Till et al., 1990). It has been Ltd
previously shown in animal models that the antioxidant enzyme superoxide dismutase provides protection from tissue injury mediated by superoxide anion (Johnson and Ward, 1981; McCormick et al., 1981). The present study, a phase I clinical trial, investigated the effect of the stabilized antioxidant enzyme, polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), on plasma-conjugated dienes in thermally injured human patients.
Materials and methods Informed consent was obtained from 12 burn patients admitted to this Bum Centre. These burn patients ranged in age from 20 years to 73 years and the extent of burn ranged from 14 per cent to 45 per cent total body surface area (Tub&I). Immediately after admission and within 6 h postburn, these patients were given a single, intravenous dose of PEG-SOD (Enzon, Inc., South Plainfield, NJ, USA). The first six patients received 5OOunits PEG-SOD/kg of body weight and the other six patients received 1000 units/kg. Blood samples were collected prior to PEG-SOD admiistration and every 6 h initially, every 12 h for 2 days and then every 24 h thereafter for up to 200 h postbum. These blood samples were collected in tubes containing 10 ITIMethylene diamine tetra-acetic acid. Samples were kept on ice and plasma was immediately separated by centrifugation at 4’C and 3ooO rev./min. Plasma was then frozen at - 70°C until assayed. Products of lipid peroxidation (conjugated dienes) were extracted from these plasma samples in chloroformmethanol, dried under nitrogen and resuspended in heptane for absorption measurements using a previously described method (Till et al., 1985; Ward et al., 1985). These extracts were subjected to spectrophotometric analysis at 233 nm. Absorbance data for samples collected from each time 72-120 and 120-200 h) were period (6-24,2448,48-72, compared between treatment groups and compared to plasma samples from patients who were burned but not treated with PEG-SOD. There were 24 paired samples analysed for each time period and each treatment group. Statistical analysis (Godfrey, 1985) was pexformed using
analysis of variance (ANOVA) and data were expressed as mean f standard error of the mean. Statistical significance was defined as P< 0.05 by ANOVA.
Thomson et al.: SOD in
burned patients
407
Table I.
Demographics (mean f standard error) of cotitrol burn patients and bum patients treated with a single intravenous dose of either 500 or 1000 units of PEG-SOD per kilogram of body
?a&
IL Conjugated di ene levels of bum patients with and without treatment with intravenous PEG-SOD Conjugated diene levels (absorbance at 233nmA s.e.m.‘)
weight PEG-SOD dose
PEG-SOD treated
Contror
500 units/kg’
7000 units/kg*
Mean Range
42.7h5.1 (28-60)
42.2 f 7.3 (20-58)
47.8 f 7.9 (26-73)
%TBSA burn Mean Range
40.5f 9.5 (25-79)
24.0 f 4.2 (14-43)
28.2 f 3.9 (17-45)
Age (W
TBSA, ‘n=6.
total body surface
Time after burn injuty
500 units/kg
1000 units/kg
Pre PEG-SOD Post PEG-SOD 24h 48h 72h 120h 200 h
0.61 f 0.07
0.88 f 0.35
0.62zkO.12 0.59 f 0.08’ 1.30 f 0.37 0.97 f 0.25 1.11 zto.30
0.52 f 0.13 0.55*0.13 0.39 f 0.01. 0.61 f 0.15” 0.48 f 0.08
ND, no data. *P < 0.05 compared
to control
Control
ND 1.56kO.02 1.39k 0.31 1.38*0.19 ND
area.
Results Burn patients treated with 500 units of PEG-SOD/kg showed an initial decline in plasma-conjugated dienes, but diene levels returned to control levels by 72 h postbum (TubleII). Those patients who received IO00 units PEGSOD/kg showed significantly lowered levels of plasma conjugated dienes up to 120 h postbum when compared to controls. In this group of patients, plasma diene levels remained lowered up to 200 h when compared to the group receiving 500 units/kg. A group of six non-age-matched normal volunteers showed mean plasma levels of conjugated dienes of 0.48 absorbance units. It was noted that pre PEGSOD levels of conjugated dienes were higher than normal in both bum treatment groups, and were higher in the 1000 unit/kg group than either the 500 unit/kg or control group. Treatment with 1000 unit/kg almost completely prevented the appearance of lipid peroxidation products (conjugated dienes) in the plasma of burn patients within 24 h of treatment.
Discussion These data suggest that intravenous administration of the antioxidant enzyme PEG-SOD decreases the plasma levels of lipid peroxidation products in burn patients. These data also suggest that, when administered immediately postbum, 1000 unit/kg of PEG-SOD is more effective in reducing plasma levels of conjugated dienes than is 500 unit/kg. The rise in lipid peroxides of untreated control bum patients in this study is consistent with the findings of other investigators who have shown lipid peroxide levels to rise consistently in the immediate postbum period. Although the untreated control patients had a larger mean percentage bum, ANOVA showed that the group was not significantly different from the two treatment groups. Conjugated diene levels in the untreated burns were similar to those seen in the smaller mean bum size of the 500 unit/kg group when treatment appeared to fail after 72 h. Products of lipid peroxidation are somewhat variable in nature and appear to be higher in larger bums, but do not appear to correlate with mortality probability (Gosling et al., 1988). In this patient population it was observed that the larger burns did have mean levels of dienes similar to mean levels of dienes observed in the smaller bums, however, some larger bums had single absorbance readings in excess of 4.0. These dif-
levels.
ferences in diene levels may be explained by the transient nature of the dienes, sample size or sample time. However, the data support the conclusion that PEG-SOD prevents oxygen radical-mediated conjugated diene formation. Although Demling et al. (1988) have reported that after endotoxin challenge conjugated dienes are cleared rapidly from the circulation, it appeared in these bum patients that conjugated dienes persisted for up to 8 days as shown previously by Hiramatsu and Jzawa (1984). It may be proposed that the dienes measured in this study were not the initial membrane phospholipid peroxidation products generated as the direct result of the bum injury. but were those produced by leucocytes involved in the ensuing inflammatory response (Till et al., 1983; Moore et al., 1986). There is published evidence to suggest that removal or prevention of peroxidation products lessens the inflammatory response by reducing chemoattractant lipids in injured tissue (Petrone et al., 1980). The prevention of lipid peroxidation products by elimination of superoxide anion has been shown in this study; however, it is yet to be demonstrated that this treatment has clinical relevance. Further investigation is required to determine clinical efficacy of such treatments.
References Dernling R. H., Lalonde C., Ryan P. et al. (1988)
Endotoxemia
produces an increase in arterial but not venous lipid peroxides in sheep.]. Appl.Physiol, 64, 592. Godfrey K. (1985) StaMics in practice comparing the means of several groups. N. Engl. J Med. 313, Gosling
P., Sukliffe
A.
1450.
J.,Cooper M. A. C. S. et
al. (1988)
Burnand
trauma associated proteinuria: the role of lipid peroxidation, renin and myoglobin. Ann. Clin.Biuch. 25,53. Hiramatsu M. and Izawa Y. (1984) Serum lipid peroxide levels of patients suffering thermal injury. Bums 11,111. Johnson K. J. and Ward P. A. (1981) Role of oxygen metabolites in immune complex injury of lung. _I.Immun01. 126‘2365.
McCormick J. R., Harkin M. M., Johnson, K. J. et al. (1981)
Sup-
pression by superoxide dismutase of immune-complex-induced puhnonary alveolitis and dermal infknmation. Am. J P&d 102,
55.
Moore F. D., Davis C., Rodrick M. et al. (1986) Neutrophil activation in thermal injury as assessed by increased expression of complement receptors. New Engl. J A/lad. 314,948.
Bums (1990) Vol. 16/No.
408
Petrone W. F., English D. K., Wong K. et al. (1980) Free radicals and inflammation: the superoxide dependent activation of a neutrophil chemotactic factor in plasma. Proc. Nutl. Aced. So. USA 77, 1159. Recknagel R. 0. and Ghoshal A. K. (1966) Lipoperoxidation as a vector in carbon tetrachloride hepatotoxicity. Lab. Inmt. 15, 132. Romaschin A. D., Rebeyka I., Wilson G. J. et al. (1987) Conjugated dienes in ischemic and reperfused myocardium: an in vivo chemical signature of oxygen free radical mediated injury. J. Mol. Cell. CardioJ. 19, 289. Till G. O., Beauchamp C., Menapace D. et al. (1983) Oxygen radical dependent lung damage following thermal injury of rat skin. J. Trauma 23,269. Till G. O., Hatherill J. R., Tourtellotte W. W. et al. (1985) Lipid peroxidation and acute lung injury after thermal trauma to skin. Am. J. Pafhol. 119, 376.
Till G. O., Friedl H. P. and Ward P. A. (1990) Phagocytic cellmediated injury: relationship to ischemic injury. In: Zelenock G. B. (ed.), Clinical lschetnic Syndromm Mechanism and Consequolces of Time Injury. St Louis, Mosby, pp. 327-345. Ward P. A., Till G. O., Hatherill J. R. et al. (1985) Systemic complement activation, lung injury and products of lipid peroxidation. J. Chn. haed. 76, 517. Woolliscroft J. O., Prasad J. K., Thomson P. D. et al. (1990) Metabolic alterations in burn patients: detection of adenosine triphosphate degradation products and lipid peroxides. Bums 16, 92.
Paper accepted
15 June 1990.
Correspondenceshould be uddd to: Dr P. D. Thomsom, University of Michigan Bum Center, lC435/0033 University of Michigan Hospital, Ann Arbor, MI 48109, USA.
BritishAssociation of PlasticSurgeons Advanced Courses in PlasticSurgery The sixth meeting of the above course will be held on Trauma of the Upper Limbs/Peripheral Nerve Surgery at Mount Vernon Hospital, Northwood on 819 Fetiruary 1991. The seventh meeting will be held on Lower Limb Trauma/Lymphoedema/Leg Ulcers in Bristol on 8/9 April 1991. The eighth meeting of the above course will be held on Burns in Mar&ester on 17/18 July 1991. The courses are aimed at consultants and trainees in plastic surgery but readers of Bum are invited to attend. The fee will be E200 which includes one night’s accommodation and all meals. Further details and an application form: British Association of Plastic Surgeons, The Royal College of Surgeons of England, 3543 Liicoln’s Inn Fields, London WCZA 3PN. Tel: 071-831-516112;
6
Fax 071-8314041.
3rd Congress on Bum Treatment Kosice, Czechoslovakia 13-14 June 1991 The main topics of the meeting will be: 0 Prevention ??Reconstruction and Rehabilitation of Burns 0 Inununology 0 Disaster Planning. The meeting will coincide with the 20th anniversary of the Burn Centre in Kosice. For information please contact: JaroslavBlaha, M.D., President of Congress, Centre for Bum Treatment, and Reconstructive Surgery, ZUNZ Kosice-Saca 04453, Czechoslovakia.
