A nurse-led paediatric oncology fast-track clinic proves a successful ambulatory intervention for patients.

AIM: To assess the impact of a pilot nurse-led paediatric oncology fast-track clinic (OFTC) for complications and side effects following chemotherapy within a paediatric tertiary hospital. METHODS: Prospective clinical data from the first 100 patients seen in the OFTC were compared with retrospective data of oncology patient presentations to the emergency department (ED) (over a 1-year period, n = 196) who would have been eligible for review in the OFTC. Parent and patient satisfaction of clinical care were also assessed via surveys pre- and post-OFTC implementation. RESULTS: Analysis which achieved statistical difference was a reduction in the number of blood tubes taken in OFTC (average 1.9 for those discharged from clinic, 2.9 for those admitted from clinic) in comparison to those seen in the ED (average 3.2) (p = 0.0027). The average number of interventions per patient seen in the ED were 2.1 (standard deviation 1.64) compared with 1.7 (standard deviation 1.55) interventions per patient seen in the OFTC, and who were not admitted following review. This result approached statistical significance with p = 0.0963. Other results which did not meet statistical significance included a reduction in treatment times, hospital admissions and medical oncology reviews. CONCLUSION: Our pilot study implementing an OFTC for the triage and assessment of chemotherapy-related complications has proven successful from an operational and consumer perspective. The clinic improved care by ensuring expedited review, more streamlined interventions, and less overall hospital admissions. The improvements in efficiency were also mirrored by increased parent and patient satisfaction.

Clinical management of Australian adolescents and young adults with acute lymphoblastic and myeloid leukemias: A national population-based study.

BACKGROUND: While several studies have examined the treatment of adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL), studies of acute myeloid leukemia (AML) are rare. Using national data for Australia, we describe (i) the number and type of treatment centers caring for AYAs, (ii) induction/first-line treatments, and (iii) survival outcomes. PROCEDURE: National population-based study assessing treatment of 15- to 24-year-olds diagnosed with ALL or AML between 2007 and 2012. Treatment details were abstracted from hospital medical records. Treatment centers were classified as pediatric or adult (adult AYA-focused or other adult; and by AYA volume [high/low]). Cox proportional hazard regression analyses examined associations between treatment and overall, event-free, and relapse-free survival outcomes. RESULTS: Forty-seven hospitals delivered induction therapy to 351 patients (181 ALL and 170 AML), with 74 (21%) treated at pediatric centers; 70% of hospitals treated less than two AYA leukemia patients per year. Regardless of treatment center, 82% of ALL patients were on pediatric protocols. For AML, pediatric protocols were not used in adult centers, with adult centers using a non-COG 7+3-type induction protocol (51%, where COG is Cooperative Oncology Group) or an ICE-type protocol (39%, where ICE is idarubicin, cytarabine, etoposide). Exploratory analyses suggested that for both ALL and AML, AYAs selected for adult protocols have worse overall, event-free, and relapse-free survival outcomes. CONCLUSIONS: Pediatric protocols were commonly used for ALL patients regardless of where they are treated, indicating rapid assimilation of recent evidence by Australian hematologists. For AML, pediatric protocols were only used at pediatric centers. Further investigation is warranted to determine the optimal treatment approach for AYA AML patients.

Inconsistencies and time delays in site-specific research approvals hinder collaborative clinical research in Australia.

BACKGROUND/AIM: The aim of this study was to describe the time and documentation needed to gain ethics and governance approvals in Australian states with and without a centralised ethical review system. METHODS: This is a prospective descriptive study undertaken between February 2012 and March 2015. Paediatric and adult hospitals (n = 67) in Australian states were approached to allow the review of their medical records. Participants included 15- to 24-year-olds diagnosed with cancer between 2008 and 2012. The main outcomes measures were time (weeks) to approval for ethics and governance and the number and type of documents submitted. RESULTS: Centralised ethics approval processes were used in five states, with approval taking between 2 and 18 weeks. One state did not use a centralised process, with ethics approval taking a median of 4.5 weeks (range: 0-15) per site. In four states using a centralised ethics process, 33 governance applications were submitted, with 20 requiring a site clinician listed as an investigator. Governance applications required the submission of 11 documents on average, including a Site-Specific Assessment form. Thirty-two governance applications required original signatures from a median of 3.5 (range: 1-10) non-research persons, which took a median of 5 weeks (range: 0-15) to obtain. Governance approval took a median of 6 weeks (range: 1-45). Twelve research study agreements were needed, each taking a median of 7.5 weeks (range: 1-20) to finalise. CONCLUSION: The benefits of centralised ethics review systems have not been realised due to duplicative, inflexible governance processes. A system that allowed the recognition of prior ethical approval and low-risk applications was more efficient than a central ethics and site-specific governance process.

Adolescents and young adult cancer survivors: exercise habits, quality of life and physical activity preferences.

INTRODUCTION: Given the decades of survivorship for adolescent and young adult (AYA) cancer survivors, it is important to promote behaviours that enhance physical and mental well-being and quality of life (QoL). The purpose of this study was to explore the exercise programming preferences and information needs of AYA survivors and to examine the impact of a cancer diagnosis on physical activity behavior and QoL. METHODS: Participants aged 15-25 years at time of diagnosis and referred to a specialist AYA cancer service between January 2008 and February 2012 were recruited. Eligible participants were mailed a self-administered questionnaire assessing demographic and disease-related information, physical activity levels over time and exercise information preferences. QoL was measured using the Assessment of Quality of Life-6D (AQoL-6D). RESULTS: Seventy-four (response rate 52 %) participants completed the questionnaire. The mean age was 23 years with 54 % female, with prevalent diagnoses included hematological malignancy (45 %) and sarcoma (24 %). Results indicated a significant reduction in the average minutes of physical activity post diagnosis (p =< 0.001) and during treatment (p = < 0.001). AYA who met public health physical activity guidelines (n = 36) at questionnaire completion had significantly higher QoL than those not meeting the guidelines (n = 38) (median (Mdn) = 0.87, interquartile range (IQR) = 0.73 to 0.98 and Mdn = 0.81, IQR = 0.57 to 0.93, respectively; p = 0.034). Most participants wanted exercise information at some point after diagnosis (85 %) but many did not receive any information (45 %). CONCLUSIONS: Findings suggest that AYA with cancer experience a significant impact on physical activity levels and QoL. Moreover, survivors experience considerable difficulty returning to premorbid levels of activity. Our study suggests that interventions promoting physical activity and healthy lifestyle behaviours would be well accepted within this population and may be essential to improve their long-term health and QoL during survivorship.

Factors influencing the documentation of fertility-related discussions for adolescents and young adults with cancer.

PURPOSE: A cancer diagnosis and treatment may have significant implications for a young patient's future fertility. Documentation of fertility-related discussions and actions is crucial to providing the best follow-up care, which may occur for many years post-treatment. This study examined the rate of medical record documentation of fertility-related discussions and fertility preservation (FP) procedures for adolescents and young adults (AYAs) with cancer in Australia. METHODS: A retrospective review of medical records for 941 patients in all six Australian states. Patients were identified through population-based cancer registries (four states) and hospital admission lists (two states). Trained data collectors extracted information from medical records using a comprehensive data collection survey. Records were reviewed for AYA patients (aged 15-24 years at diagnosis), diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia, central nervous system (CNS) tumours, soft tissue sarcomas (STS), primary bone cancer or Ewing's family tumours between 2007 and 2012. RESULTS: 47.2% of patients had a documented fertility discussion and 35.9% had a documented FP procedure. Fertility-related documentation was less likely for female patients, those with a CNS or STS diagnosis and those receiving high-risk treatments. In multivariable models, adult hospitals with an AYA focus were more likely to document fertility discussions (odds ratio[OR] = 1.60; 95%CI = 1.08-2.37) and FP procedures (OR = 1.74; 95%CI = 1.17-2.57) than adult hospitals with no AYA services. CONCLUSIONS: These data provide the first national, population-based estimates of fertility documentation for AYA cancer patients in Australia. Documentation of fertility-related discussions was poor, with higher rates observed in hospitals with greater experience of treating AYA patients.

Metabolic response to insulin and glucose infusions in starved tumor-bearing rats.

Tumor-induced alterations in insulin sensitivity and glucose metabolism were investigated by examining the effect of glucose and insulin infusions in 72-h-starved tumor-bearing (TB) rats. Following glucose infusion, the rate of glucose disappearance from the blood was similar in TB and non-tumor-bearing (NTB) rats, even though insulin concentrations were lower in TB rats. Blood lactate was increased in TB rats prior to treatment and increased immediately following glucose infusion. Insulin alone decreased blood glucose in NTB but not TB rats. When insulin was infused together with glucose, the rate of glucose disappearance increased similarly in both TB and NTB rats. The immediate increase in blood lactate seen in TB rats following glucose infusion was not apparent in the TB rats receiving insulin and glucose. TB rats infused with glucose and insulin showed a greater rise in blood alanine concentrations, compared with all other infusion regimens. While ketone body concentrations decreased in both TB and NTB rats in response to the different infusion regimens, plasma free fatty acids in TB rats were not decreased by insulin and glucose treatments. TB rats therefore not only have decreased insulin release, but adipose tissue is also less sensitive to insulin action. In vivo studies using 2-deoxy[U-14C]glucose showed that glucose uptake by the muscle and adipose tissue, but not the tumor, was significantly increased by the infusion of insulin, thereby demonstrating one of the mechanisms by which insulin may act to conserve host tissue.

Alterations in beta-adrenoceptors and polyploidy in cultured aortic smooth muscle cells from different age groups of spontaneously hypertensive rats and Wistar-Kyoto rats.

OBJECTIVE: The relationship between the number of beta-adrenoceptors and polyploidy in cultured aortic smooth muscle cells derived from different age groups of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were examined. DESIGN: The number of beta-adrenoceptors, the percentage of multinucleated cells and the incidence of polyploidy from cultured smooth muscle cells derived from SHR and WKY rats aged 3-4, 10-12 and 28-30 weeks were measured. The effect of passaging of the cells on the expression of beta-adrenoceptors and polyploidy on cultured smooth muscle cells from both SHR and WKY rats was also investigated. METHODS: Receptor binding experiments were carried out using [125]-monoiodocyanopindolol with osmotically lysed cultured aortic smooth muscle cells to investigate the properties of vascular beta-adrenoceptors in SHR and WKY rats. The proportion of polyploid smooth muscle cells was determined by frequency distribution analyses of Feulgen DNA microdensitometric measurements. RESULTS: The incidence of polyploid smooth muscle cells was consistently higher in cells cultured from SHR than in those from WKY rats in all three age groups, with a positive correlation between polyploidy and age in SHR. Furthermore, in all three age groups the number of beta-adrenoceptor binding sites was also higher in cultured smooth muscle cells from SHR than in those from WKY rats. There was no significant difference in the receptor affinity. The increase in beta-adrenoceptor number was associated with an increase in polyploidy, and both of these changes were positively correlated both with the age of the rats from which these cells were derived and with the number of passages. CONCLUSIONS: Under cell culture conditions the expression of beta-adrenoceptor density increases with the number of passages in both SHR and WKY rats. Smooth muscle cells derived from older SHR and WKY rats have a greater propensity to develop polyploidy. This trend is significantly accelerated in cultured smooth muscle cells derived from SHR compared with those from WKY rats, suggesting a premature ageing process. These findings suggest that, in cultured smooth muscle cells from SHR and WKY rats, beta-adrenoceptors may influence the expression of polyploidy.

Differing protection with aspartate and glutamate cardioplegia in the isolated rat heart.

Aspartate and glutamate each have been shown to improve cardiac recovery after hypoxia or ischemia under normothermic conditions, but whether their effects are additive and to what extent they are modified by hypothermia has not been studied systematically. We set out to compare the individual and combined protective effects of aspartate and glutamate during cardioplegic arrest under normothermic and hypothermic conditions in the rat. Using isolated working rat hearts, functional and metabolic recovery was assessed after 0.5 hours of potassium arrest at 37 degrees C or 5 hours at 2 degrees C in control hearts (C) and in hearts in which 20 mmol/L glutamate (G), 20 mmol/L aspartate (A), or both (A + G) was added to the cardioplegic solution. Under normothermic conditions, percentage recovery of prearrest work (mean +/- standard error of the mean) was as follows: C = 31.7 +/- 2.8, G = 34.8 +/- 0.2, A = 49.6 +/- 2.8*, A + G = 53.7 +/- 2.3*. Under hypothermic conditions, the values were as follows: C = 40.4 +/- 4.0, G = 45.2 +/- 2.3, A = 59.4 +/- 1.8*, A + G = 54.1 +/- 1.2* (*p < 0.01 versus C and G). Recovery of postischemic high-energy phosphate content followed the same pattern: A = A + G > G or C. Measurement of postischemic myocardial content of amino acids showed that recovery of function and energy status correlated with maintenance of myocardial levels of aspartate (r = 0.9; p < 0.01) but not glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressed function in remote myocardium after myocardial infarction: influence of orotic acid.

BACKGROUND: We have previously shown that infarction impairs recovery of global function after subsequent cardioplegic arrest and that therapy with orotic acid improves recovery. The aim of this study was to measure the effect of infarction on regional and global left ventricular function and to determine whether orotic acid exerts a beneficial effect exclusive of the effects of cardioplegia. METHODS: Acute myocardial infarction was produced in dogs. They then received either orotic acid or placebo (control) orally (n = 12 per group). Fractional radial shortening and systolic wall thickening were measured by two-dimensional echocardiography before and 1 and 3 days after infarction with and without beta-adrenergic blockade, and in 6 dogs up to 9 days after infarction. Global function was measured under anesthesia 4 days after infarction. RESULTS: In control animals, fractional radial shortening in the infarct decreased from 20.6% +/- 5.1% before infarction to 3.0% +/- 2.2% at day 1 and to 1.9% at day 3 (p < 0.01). In the border zone radial shortening declined from 21.9% +/- 3.7% to 11.0% +/- 2.3% at day 1 and 9.3% +/- 2.8% at day 3 (p < 0.05). In the noninfarcted myocardium radial shortening also declined from 27.1% +/- 1.9% before infarction to 18.3% +/- 2.3% on day 1 (p < 0.05) and to 16.0% +/- 2.8% on day 3 after infarction (p < 0.05) with recovery to preinfarct levels by 9 days after infarction. These findings were confirmed by measurements of systolic thickening. Before infarction beta-receptor blockade decreased fractional shortening in all regions of the left ventricle, but this effect was absent on day 3 after infarction, implying that the myocardium had become less responsive to beta-adrenergic stimulation. Measurements of global function 4 days after infarction showed marked depression of stroke work. There was no effect of orotic acid treatment on regional or global function. CONCLUSIONS: Myocardial infarction causes reversible depression of resting function and beta-adrenergic responsiveness in the remote and border zone areas, which is not prevented by metabolic therapy with orotic acid. This finding may explain the adverse response of the infarcted heart to cardioplegic arrest.

Continuous perfusion improves preservation of donor rat hearts: importance of the implantation phase.

BACKGROUND: Continuous hypothermic perfusion of donor hearts may provide extra protection for long ischemic times and suboptimal donors. The aim of three separate studies was to assess the effect of continuous hypothermic perfusion during simulated donor heart storage and implantation. METHODS: In study 1 twelve isolated rat hearts underwent 10 minutes of normothermic ischemia to simulate the effect of brain death on the heart and 5 hours of cardioplegic arrest, using University of Wisconsin solution. Six hearts were statically stored in University of Wisconsin solution at 2 degrees C, and six were perfused with University of Wisconsin solution. To assess the effect of simulated implantation, in study 2 an additional 12 hearts were statically stored for 5.5 hours in University of Wisconsin solution, six of which were rewarmed to a mean of 16 degrees C over the last 30 minutes of arrest. To assess the effect of simulated perfusion, in study 3 during implantation 12 hearts were rewarmed to a mean of 16 degrees C over the last 30 minutes of arrest, during which time six were perfused with 2 degrees C solution. RESULTS: Hearts perfused during storage demonstrated greater recovery of prearrest power, 85.8% +/- 1.8%, than hearts preserved by static storage, 72.7% +/- 3.0% (p < 0.01). The simulated warm implantation period reduced recovery of power from 68.3% +/- 5.1% to 40.2% +/- 2.0% (p < 0.001). Perfusion during warm implantation improved recovery to 61.8% +/- 3.9% (p < 0.01). In all experiments improved function was accompanied by improved metabolic energy status. CONCLUSIONS: During the implantation period of heart transplantation the donor heart sustains injury that could amount to 50% of total ischemic injury. Continuous perfusion during the cold storage phase and during simulated implantation improves recovery of the donor heart.

Comparison of UW solution and St. Thomas' solution in the rat: importance of potassium concentration.

BACKGROUND: University of Wisconsin solution (UW) is in limited clinical use for heart transplantation, but there are doubts about its efficacy and concerns about the effect of its high K+ concentration on endothelium. St. Thomas' solution with or without aspartate is widely used and is of proven efficacy. METHODS: Using a modified (starch-free) variant of UW (MUW) we studied: (1) recovery of function with UW compared with aspartate-containing St. Thomas' solution; (2) effect of elevation of K+ in St. Thomas' solution to the level in UW; and (3) effect of reduction of K+ in UW and addition of Ca2+ or aspartate. Isolated rat hearts underwent 7 hours of arrest at 1 degrees C using MUW with or without 20 mmol/L aspartate or using aspartate-containing St. Thomas' solution. RESULTS: Functional recovery with MUW (51.8% +/- 2.5%) was superior to that with aspartate-containing St. Thomas' solution (37.1% +/- 4.3%; p < 0.01). Addition of aspartate to MUW had no effect. During 6 hours of arrest, lowering the K+ in MUW from 125 mmol/L to 20 mmol/L reduced functional recovery from 59.9% +/- 4.2% to 42.3% +/- 4.3% (p < 0.01). The addition of 1 mmol/L Ca2+ had no effect. Elevation of K+ in St. Thomas' solution produced more rapid arrest but no improvement in recovery. CONCLUSIONS: The protective effect of starch-free UW is greater (+13%) than that of aspartate-enriched St. Thomas' solution. Reduction of K+ in UW to lessen possible deleterious effects would decrease its protective effect by about 30% to a level comparable with that of St. Thomas' solution.

Creatine kinase reference intervals determined from a multi-centre data pool.

Reference intervals for creatine kinase assayed at 37 degrees C using N-acetyl cysteine-activated methods have been determined on data obtained from 10 laboratories throughout Australia. The pooled distributions for males and females are skewed towards higher values and cannot be transformed to Gaussian distributions. The reference interval for females was calculated to be 34 to 180 U/l and for males it was 46 to 300 U/l. However, if creatine kinase is to be used in the diagnosis of myocardial infarction, the upper limit of the reference interval for males is considered to be too high. It is concluded that for males, the upper limit may need to be determined on specific populations such as hospital inpatients.

The effect of orotic acid on the response of the recently infarcted rat heart to hypothermic cardioplegia.

Patients with a recent myocardial infarction have a higher morbidity and mortality than comparable patients with chronic myocardial ischaemia. We postulated that this might be due to a reduced overall tolerance of the heart to cardioplegic arrest in the presence of a recent infarct. We postulated that orotic acid, a pyrimidine precursor which augments the rate of protein synthesis, might improve the response of the recently infarcted heart to cardioplegic arrest. Myocardial infarction was produced in rats by coronary ligation. The rats were then divided into two groups according to whether they were treated with oral orotic acid (10 mg/kg per day) or untreated. A sham-operated (non-infarcted) group served as normal controls. After 2 days, the hearts (n = 12 per group) underwent 1 h of cardioplegic arrest at 23 degrees C on the isolated working heart apparatus. Before arrest, maximum cardiac function in the untreated infarct group was lower than in the normal group (P less than 0.05), whereas in the treated group, function was similar to the normal group. After arrest there was severe depression of cardiac function in the untreated infarct group: only 57% recovery of the pre-arrest value compared with 86% in the normal group (P less than 0.001). In the orotic acid treated group, recovery (90%) was significantly greater than in the untreated group (P less than 0.001) and equivalent to the normal group. Oxygen utilisation, when corrected for external work, was higher in both infarct groups than in the normal group before and after arrest (P less than 0.05 in both cases). Total uridine nucleotide content of the infarcted and non-infarcted zones of the heart was increased. Treatment with orotic acid produced a further upward trend in uridine nucleotide levels. We conclude that an established, recent infarct reduces the overall tolerance of the heart to hypothermic cardioplegia. Treatment with orotic acid improves the function of the infarcted heart following cardioplegic arrest, and may therefore improve the results of urgent cardiac surgery in patients with myocardial infarction.

The effect of dietary refined sugars and sugar alcohols on renal calcium oxalate deposition in ethylene glycol-treated rats.

The effect of administering refined carbohydrates in the diet on calcium oxalate deposition in the kidneys of rats given 1% (v/v) ethylene glycol in their drinking-water was investigated. The rats were given 0, 2.5, 10, 30 or 60% sucrose in the feed (w/w) and/or drinking-water (w/v) or 20% (w/w) starch, glucose, sucrose, fructose, galactose, xylitol or sorbitol in the feed for 3 wk. All of the animals remained healthy over the test period as far as could be assessed by the measurement of 19 plasma biochemical parameters. The inclusion of 30 or 60% (w/w) sucrose in the diet resulted in a more than tenfold increase in the deposition of calcium oxalate in the kidneys. However, this deposition could not be predicted from data on urinary pH and urinary excretion of calcium, oxalate and urate, which have been reported to be risk factors for stone formation. There was no evidence of increased rates of oxalate production from ethylene glycol. The administration of fructose, xylitol or sorbitol was associated with the greatest renal deposition of calcium oxalate, and glucose was associated with by far the least.

The long-term effect of dietary administration of refined sugars and sugar alcohols on plasma biochemistry, urine biochemistry and tissue histology in mice given a limited degree of dietary self-selection.

A prototype animal feeding model is described in which mice were meal-fed a balanced diet but were given free access to water (controls) or 20% (w/v) solutions of glucose, sucrose, fructose, xylitol or sorbitol. Under these conditions it was found that the provision of an alternative energy source, in the form of a refined carbohydrate, produced marked effects on total energy intake, mouse cube (i.e. balanced energy) intake and body weight. There were also changes in the metabolic states of the animals as assessed by serum levels of glucose, urea and cholesterol, plasma levels of lactate and D-3-hydroxybutyrate, and urinary excretion of urea and oxalate. Histological examinations of tissue indicated that the sucrose-fed mice had a tendency to suffer from acute congestion of the lungs and liver steatosis. Given a limited degree of dietary self-selection it appears that mice are more likely to be at risk of excessive food consumption and obesity when given glucose- or sucrose-containing diets than they are when fructose-, xylitol- or sorbitol-containing diets are given.

Change and stability in cellular organisms.

The living cell is characterized by both its potential for change and its tendency towards a stable state. The interaction between the DNA information system and the metabolic steady state is described. A model based on this interaction leads to the conclusions that change can only be initiated from the environment but that the direction of any change is determined by the cell.

Some thoughts on evolution.

The sparsity of transitional forms and the abrupt appearance of higher taxa in the fossil record are enigmas for the neo-Darwinian theory of evolution. If the cell is considered to be a steady state system then mutations affecting non-regulatory proteins will have far less effect on the steady state than mutations affecting regulatory proteins. This latter type of mutation, when expressed in multicellular biological systems, is a sufficient explanation for the discontinuities observed between species. Such a mechanism, however, has its own implications for any theory of evolution.

Do burn patients have a silver lining?

Silver-containing pharmacological preparations have been used for many years in the prophylaxis and management of burn wound sepsis and, more recently, 1 per cent silver sulphadiazine cream (SSD) has been the treatment of choice for such problems. A prospective clinical study has been undertaken to determine the absorption and effects of the silver ion from SSD, with particular reference to hepatic and renal function. Twenty-two patients were studied. The silver assay was done by atomic absorption spectrophotometry with an attached graphite furnace. The detection level was 0.5 micrograms/l. The precision at 3.5 micrograms/l was 4.8 per cent and at 8.5 micrograms/l was 2.8 per cent. Silver was rapidly absorbed through the burn wound and serum silver levels were elevated in 20 patients. Silver was found to be deposited biochemically and electronmicrographically in the liver and kidneys of the only patient who died in the study group. Early hepatic dysfunction was present in all burns greater than 10 per cent total body surface area. Liver and renal function tests did not correlate with serum silver levels. A urinary threshold to silver excretion was seen at a serum silver level of 100 micrograms/l. This study demonstrates that silver is rapidly absorbed through burn wounds, is deposited in large amounts throughout the body but appears safe when used in the treatment of moderate burns. Whether the very high levels recorded in the subject who died were inherently detrimental will remain a matter for speculation.