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1.  Critical dependence of acetate thermal mattress on gel activation temperature 
Sodium acetate gel mattresses provide an active method of warming patients through release of latent heat of crystallisation. They can be used as an adjunct to incubator care or as an exclusive heat source.
To determine activation temperatures of the Transwarmer mattress needed to achieve plateau temperatures of 38–42°C.
Design and setting
In vitro testing of mattress temperature.
Methods and outcome measures
Transwarmer mattresses were activated at initial temperatures ranging from 5 to 40°C. Mattress temperature was recorded up to 4 h to determine peak and plateau temperatures. Peak and plateau temperatures achieved by the mattress were related to the initial starting temperature.
The starting temperature of the mattress was strongly correlated with peak and plateau temperature (r = 0.99, p<0.001). To achieve the target temperature of 38–42°C, the Transwarmer mattress requires activation between 19.2°C and 28.3°C. A temperature of 37°C could be generated by activation at 17°C.
Safe use of this device is critically dependent on gel temperature at the point of activation. To ensure warming of a hypothermic neonatal patient without running any risk of burns, the mattress should be activated with a gel temperature between 19°C and 28°C.
PMCID: PMC2675300  PMID: 16877478
2.  Effect evaluation of a heated ambulance mattress-prototype on body temperatures and thermal comfort - an experimental study 
Exposure to cold temperatures is, often, a neglected problem in prehospital care. One of the leading influences of the overall sensation of cold discomfort is the cooling of the back. The aim of this study was to evaluate the effect of a heated ambulance mattress-prototype on body temperatures and thermal comfort in an experimental study.
Data were collected during four days in November, 2011 inside and outside of a cold chamber. All participants (n = 23) participated in two trials each. In one trial, they were lying on a stretcher with a supplied heated mattress and in the other trial without a heated mattress. Outcomes were back temperature, finger temperature, core body temperature, Cold Discomfort Scale (CDS), four statements from the state-trait anxiety – inventory (STAI), and short notes of their experiences of the two mattresses. Data were analysed both quantitatively and qualitatively. A repeated measure design was used to evaluate the effect of the two mattresses.
A statistical difference between the regular mattress and the heated mattress was found in the back temperature. In the heated mattress trial, the statement “I am tense” was fewer whereas the statements “I feel comfortable”, “I am relaxed” and “I feel content” were higher in the heated mattress trial. The qualitative analyses of the short notes showed that the heated mattress, when compared to the unheated mattress, was experienced as warm, comfortable, providing security and was easier to relax on.
Heat supply from underneath the body results in increased comfort and may prevent hypothermia which is important for injured and sick patients in ambulance care.
PMCID: PMC4131165  PMID: 25103366
Thermal comfort; Cold discomfort; Cold exposure
3.  The Bair Hugger patient warming system in prolonged vascular surgery: an infection risk? 
Critical Care  2003;7(3):R13-R16.
Use of the Bair Hugger forced-air patient warming system during prolonged abdominal vascular surgery may lead to increased bacterial contamination of the surgical field by mobilization of the patient's skin flora.
This possibility was studied by analyzing bacterial content in air and wound specimens collected during surgery in 16 patients undergoing abdominal vascular prosthetic graft insertion procedure, using the Bair Hugger patient warming system. The bacterial colony counts from the beginning and the end of surgery were compared, and the data analyzed using the Wilcoxon matched pairs test.
The results showed not only that there was no increase in bacterial counts at the study sites, but also that there was a decrease (P < 0.01) in air bacterial content around the patient and in the operating theatre after prolonged use of the patient warmer. No wound or graft infections occurred.
The use of this warming system does not lead to increased bacterial contamination of the operating theatre atmosphere, and it is unlikely to affect the surgical field adversely.
PMCID: PMC270670  PMID: 12793885
air microbiology; human; intraoperative care; operating rooms; surgical wound infection
4.  Core temperatures during major abdominal surgery in patients warmed with new circulating-water garment, forced-air warming, or carbon-fiber resistive-heating system 
Journal of Anesthesia  2011;26(2):168-173.
It has been reported that recently developed circulating-water garments transfer more heat than a forced-air warming system. The authors evaluated the hypothesis that circulating-water leg wraps combined with a water mattress better maintain intraoperative core temperature ≥36°C than either forced-air warming or carbon-fiber resistive heating during major abdominal surgery.
Thirty-six patients undergoing open abdominal surgery were randomly assigned to warming with: (1) circulating-water leg wraps combined with a full-length circulating-water mattress set at 42°C, (2) a lower-body forced-air cover set on high (≈43°C), and (3) a carbon-fiber resistive-heating cover set at 42°C. Patients were anesthetized with general anesthesia combined with continuous epidural analgesia. The primary outcome was intraoperative tympanic-membrane temperature ≥36°C.
In the 2 h after anesthesia induction, core temperature decreased 1.0 ± 0.5°C in the forced-air group, 0.9 ± 0.2°C in the carbon-fiber group, and 0.4 ± 0.4°C in the circulating-water leg wraps and mattress group (P < 0.05 vs. forced-air and carbon-fiber heating). At the end of surgery, core temperature was 0.2 ± 0.7°C above preoperative values in the circulating-water group but remained 0.6 ± 0.9°C less in the forced-air and 0.6 ± 0.4°C less in the carbon-fiber groups (P < 0.05 vs. carbon fiber).
The combination of circulating-water leg wraps and a mattress better maintain intraoperative core temperature than did forced-air and carbon-fiber warming systems.
PMCID: PMC3328673  PMID: 22189652
Temperature; Hypothermia; Circulating-water garment; Carbon fiber; Forced air
5.  Evaluation of bacterial contamination on surgical drapes following use of the Bair Hugger® forced air warming system 
The Canadian Veterinary Journal  2013;54(12):1157-1159.
This pilot study determined the rate of bacterial contamination on surgical drapes of small animal patients warmed intra-operatively with the Bair Hugger® forced air warming system compared to a control method. Surgical drapes of 100 patients undergoing clean surgical procedures were swabbed with aerobic culturettes at the beginning and end of surgery. Samples were cultured on Trypticase soy agar. Contamination of the surgical drapes was identified in 6/98 cases (6.1%). There was no significant difference in the number of contaminated surgical drapes between the Bair Hugger® and control groups (P = 0.47).
PMCID: PMC3831391  PMID: 24293676
6.  Accumulation and transport of microbial-size particles in a pressure protected model burn unit: CFD simulations and experimental evidence 
Controlling airborne contamination is of major importance in burn units because of the high susceptibility of burned patients to infections and the unique environmental conditions that can accentuate the infection risk. In particular the required elevated temperatures in the patient room can create thermal convection flows which can transport airborne contaminates throughout the unit. In order to estimate this risk and optimize the design of an intensive care room intended to host severely burned patients, we have relied on a computational fluid dynamic methodology (CFD).
The study was carried out in 4 steps: i) patient room design, ii) CFD simulations of patient room design to model air flows throughout the patient room, adjacent anterooms and the corridor, iii) construction of a prototype room and subsequent experimental studies to characterize its performance iv) qualitative comparison of the tendencies between CFD prediction and experimental results. The Electricité De France (EDF) open-source software Code_Saturne® ( was used and CFD simulations were conducted with an hexahedral mesh containing about 300 000 computational cells. The computational domain included the treatment room and two anterooms including equipment, staff and patient. Experiments with inert aerosol particles followed by time-resolved particle counting were conducted in the prototype room for comparison with the CFD observations.
We found that thermal convection can create contaminated zones near the ceiling of the room, which can subsequently lead to contaminate transfer in adjacent rooms. Experimental confirmation of these phenomena agreed well with CFD predictions and showed that particles greater than one micron (i.e. bacterial or fungal spore sizes) can be influenced by these thermally induced flows. When the temperature difference between rooms was 7°C, a significant contamination transfer was observed to enter into the positive pressure room when the access door was opened, while 2°C had little effect. Based on these findings the constructed burn unit was outfitted with supplemental air exhaust ducts over the doors to compensate for the thermal convective flows.
CFD simulations proved to be a particularly useful tool for the design and optimization of a burn unit treatment room. Our results, which have been confirmed qualitatively by experimental investigation, stressed that airborne transfer of microbial size particles via thermal convection flows are able to bypass the protective overpressure in the patient room, which can represent a potential risk of cross contamination between rooms in protected environments.
PMCID: PMC3056797  PMID: 21371304
7.  The effect of heated breathing circuit on body temperature and humidity of anesthetic gas in major burns 
Cold and dry gas mixtures during general anesthesia cause the impairment of cilliary function and hypothermia. Hypothermia and pulmonary complications are critical for the patients with major burn. We examined the effect of heated breathing circuit (HBC) about temperature and humidity with major burned patients.
Sixty patients with major burn over total body surface area 25% scheduled for escharectomy and skin graft were enrolled. We randomly assigned patients to receiving HBC (HBC group) or conventional breathing circuit (control group) during general anesthesia. The esophageal temperature of the patients and the temperature and the absolute humidity of the circuit were recorded every 15 min after endotracheal intubation up to 180 min.
There was no significant difference of the core temperature between two groups during anesthesia. The relative humidity of HBC group was significantly greater compared to control group (98% vs. 48%, P < 0.01). In both groups, all measured temperatures were significantly lower than that after intubation.
The use of HBC helped maintain airway humidity, however it did not have the effect to minimize a body temperature drop in major burns.
PMCID: PMC3558651  PMID: 23372879
Anesthesia; Closed circuit; General anesthesia; Humidity; Hypothermia
8.  Absence of Exertional Hyperthermia in a 17 Year Old with Severe Burns 
An important safety concern when exercising burned patients is the potential for an excessive increase in core body temperature (hyperthermia = body core temperature > 39°C) during exercise.
We examined the thermoregulatory response to exercise in the heat (31°C, relative humidity 40%) in a 17 year old with a 99% total body surface area burn. A 30 minute exercise test was performed at an intensity of 75% of his peak aerobic capacity. Intestinal temperature was assessed via telemetry with an ingestible capsule. Intestinal temperature was measured pre-exercise, during, and post-exercise.
The patient completed 12 minutes of the 30 minute exercise test. Starting core temperature was 36.98 °C and increased 0.69 °C during exercise. After excercise, intestinal temperature continued to increase, but no hyperthermia was noted.
It has been reported that burned children can safely exercise at room temperature, however, the response in the heat is unknown. This patient did not develop exertional hyperthermia, which we propose is due to his low fitness level and heat intolerance. However, the potential for hyperthermia would be increased if he were forced to maintain a high relative workload in the heat. We propose that severely burned individuals should be able to safely participate in physical activities. However, the decision to stop exercising should be accepted to avoid development of exertional hyperthermia.
PMCID: PMC3924868  PMID: 19506510
thermoregulation; hyperthermia; burns; exercise
9.  Influence of support on intra-abdominal pressure, hepatic kinetics of indocyanine green and extravascular lung water during prone positioning in patients with ARDS: a randomized crossover study 
Critical Care  2005;9(3):R251-R257.
Prone positioning (PP) on an air-cushioned mattress is associated with a limited increase in intra-abdominal pressure (IAP) and an absence of organ dysfunction. The respective influence of posture by itself and the type of mattress on these limited modifications during the PP procedure remains unclear. The aim of this study was to evaluate whether the type of support modifies IAP, extravascular lung water (EVLW) and the plasma disappearance rate of indocyanine green (PDRICG) during PP.
A prospective, randomized, crossover study of 20 patients with acute respiratory distress syndrome (ARDS) was conducted in a medical intensive care unit in a teaching hospital. Measurements were made at baseline and repeated after 1 and 6 hours of two randomized periods of 6 hours of PP with one of two support types: conventional foam mattress or air-cushioned mattress.
After logarithmic transformation of the data, an analysis of variance (ANOVA) showed that IAP and PDRICG were significantly influenced by the type of support during PP with an increase in IAP (P < 0.05 by ANOVA) and a decrease in PDRICG on the foam mattress (P < 0.05 by ANOVA). Conversely, the measurements of EVLW did not show significant modification between the two supports whatever the posture. The ratio of the arterial oxygen tension to the fraction of inspired oxygen significantly increased in PP (P < 0.0001 by ANOVA) without any influence of the support.
In comparison with a conventional foam mattress, the use of an air-cushioned mattress limited the increase in IAP and prevented the decrease in PDRICG related to PP in patients with ARDS. Conversely, the type of support did not influence EVLW or oxygenation.
PMCID: PMC1175887  PMID: 15987398
10.  Assessing the Heat Stress and Establishing the Limits for Work in a Hot Mine 
The management of the mine at Mount Isa, Queensland, Australia decided to enquire into the following questions with regard to men working underground in hot conditions:
(a) Which of the various heat stress indices predicts most accurately the effects on workmen of the various heat stress factors which occur in the mine at Mount Isa?
(b) How best should the limits of heat stress be judged at which the normal 8-hour shift should be reduced to a 6-hour shift, or at which work should be stopped?
With these objects in mind, oral temperatures were measured on 86 workmen after three hours of ordinary work in the mine and also on 36 occasions on 29 volunteers after three hours of stepping on and off a stool at a work rate of 1,560 ft. lb./min. These men were studied in different environmental heat stresses over the range that occurs in the mine. Dry bulb air temperatures (D.B.), wet bulb temperatures (W.B.), velocity of air movements, and globe temperatures (G.T.) were measured in the micro-climate in which each man worked. An estimate was made of the work rate of the 86 workmen. From these estimates and measurements, the predicted 4-hourly sweat rate (P4SR) and corrected effective temperature (C.E.T.) values were determined for each heat stress condition. P4SR values varied between 0·9 and 6·5 and C.E.T. between 70° and 95°F.
Correlation coefficients were calculated between oral temperatures and W.B.s, C.E.T.s, and P4SRs and are 0·51, 0·64, and 0·75 respectively. Further analysis was confined to C.E.T. and P4SR. Plots of oral temperature on P4SR for conditions where G.T. was more than 10°F. above D.B. were found to fall well below the rest of the plots, indicating that P4SR exaggerates the effect of mean radiant temperature. These data were therefore excluded from the rest of the analysis. Regression equations were calculated for oral temperature on P4SR and for oral temperature on C.E.T. for (a) men `on the job', for (i) conditions where D.B. was more than 10°F. above W.B. and (ii) for conditions where D.B. was less than 10°F. above W.B., and (b) for men `stepping'. This analysis showed that one overall regression line can be used for all three conditions for oral temperature on P4SR, but for oral temperature on C.E.T. at least two different regression lines would be needed. Also the correlation coefficients between oral temperature and P4SR were generally higher than between oral temperature and C.E.T. For the prediction of oral temperature in the mine at Mount Isa the P4SR index is to be preferred to the C.E.T. scale.
These results indicate that the emphasis given to G.T. in the P4SR index is too great. A multi-variance analysis of the P4SR index shows that, in the middle of the range of heat stress conditions examined, a unit change in P4SR would be obtained by about the same change in W.B. and G.T. This is at variance with the present results and also with the experimental findings of the M.R.C. Climatic Physiology Unit at Singapore. It appears, therefore, that the P4SR index should be revised in this regard.
When it came to setting limits of heat stress for a 6-hour shift and for `stop-work', it was decided to base the limit for the 6-hour shift on a 1:100 probability of men reaching an oral temperature of 100·5°F. (rectal temperature of 101·5°F.) and to base the `stop work' limit on a 1:2,000 probability of reaching an oral temperature of 101·5°F. (rectal temperature of 102·5°F.). The reasons for this choice of physiological criteria are given in full in the paper. P4SR values at which these limits are reached were determined by calculating 1:100 and 1:2,000 probability belts to the overall regression line of oral temperature on P4SR. The P4SR value at the intersection of the 1:100 probability limit and the oral temperature of 100·5°F. is 3·8 and the P4SR value at the intersection of the 1:2,000 probability limit and the oral temperature of 101·5°F. is 5·0. These then are the limits of heat stress in the mine at Mount Isa for a 6-hour shift and for `stop-work'.
A simple graphical method has been developed and is in use in the mine for determining when the level of work and environmental heat stress have reached either a P4SR value of 3·8, when the shift is reduced to six hours; or, when the heat stress has reached a P4SR value of 5·0, when work is stopped.
PMCID: PMC1008619  PMID: 6073084
11.  Comparison of the efficacy of a forced-air warming system and circulating-water mattress on core temperature and post-anesthesia shivering in elderly patients undergoing total knee arthroplasty under spinal anesthesia 
Korean Journal of Anesthesiology  2014;66(5):352-357.
In the present study, we compared changes in body temperature and the occurrence of shivering in elderly patients undergoing total knee arthroplasty under spinal anesthesia during warming with either a forced-air warming system or a circulating-water mattress.
Forty-six patients were randomly assigned to either the forced-air warming system (N = 23) or circulating-water mattress (N = 23) group. Core temperature was recorded using measurements at the tympanic membrane and rectum. In addition, the incidence and intensity of post-anesthesia shivering and verbal analogue score for thermal comfort were simultaneously assessed.
Core temperature outcomes did not differ between the groups. The incidence (13.0 vs 43.5%, P < 0.05) and intensity (20/2/1/0/0 vs 13/5/3/2/0, P < 0.05) of post-anesthesia shivering was significantly lower in the forced-air system group than in the circulating-water mattress group.
The circulating-water mattress was as effective as the forced-air warming system for maintaining body temperature. However, the forced-air warming system was superior to the circulating-water mattress in reducing the incidence of post-anesthesia shivering.
PMCID: PMC4041953  PMID: 24910726
Shivering; Spinal anesthesia; Temperature
12.  The oxycoal process with cryogenic oxygen supply 
Die Naturwissenschaften  2009;96(9):993-1010.
Due to its large reserves, coal is expected to continue to play an important role in the future. However, specific and absolute CO2 emissions are among the highest when burning coal for power generation. Therefore, the capture of CO2 from power plants may contribute significantly in reducing global CO2 emissions. This review deals with the oxyfuel process, where pure oxygen is used for burning coal, resulting in a flue gas with high CO2 concentrations. After further conditioning, the highly concentrated CO2 is compressed and transported in the liquid state to, for example, geological storages. The enormous oxygen demand is generated in an air-separation unit by a cryogenic process, which is the only available state-of-the-art technology. The generation of oxygen and the purification and liquefaction of the CO2-enriched flue gas consumes significant auxiliary power. Therefore, the overall net efficiency is expected to be lowered by 8 to 12 percentage points, corresponding to a 21 to 36% increase in fuel consumption. Oxygen combustion is associated with higher temperatures compared with conventional air combustion. Both the fuel properties as well as limitations of steam and metal temperatures of the various heat exchanger sections of the steam generator require a moderation of the temperatures during combustion and in the subsequent heat-transfer sections. This is done by means of flue gas recirculation. The interdependencies among fuel properties, the amount and the temperature of the recycled flue gas, and the resulting oxygen concentration in the combustion atmosphere are investigated. Expected effects of the modified flue gas composition in comparison with the air-fired case are studied theoretically and experimentally. The different atmosphere resulting from oxygen-fired combustion gives rise to various questions related to firing, in particular, with regard to the combustion mechanism, pollutant reduction, the risk of corrosion, and the properties of the fly ash or the deposits that form. In particular, detailed nitrogen and sulphur chemistry was investigated by combustion tests in a laboratory-scale facility. Oxidant staging, in order to reduce NO formation, turned out to work with similar effectiveness as for conventional air combustion. With regard to sulphur, a considerable increase in the SO2 concentration was found, as expected. However, the H2S concentration in the combustion atmosphere increased as well. Further results were achieved with a pilot-scale test facility, where acid dew points were measured and deposition probes were exposed to the combustion environment. Besides CO2 and water vapour, the flue gas contains impurities like sulphur species, nitrogen oxides, argon, nitrogen, and oxygen. The CO2 liquefaction is strongly affected by these impurities in terms of the auxiliary power requirement and the CO2 capture rate. Furthermore, the impurity of the liquefied CO2 is affected as well. Since the requirements on the liquid CO2 with regard to geological storage or enhanced oil recovery are currently undefined, the effects of possible flue gas treatment and the design of the liquefaction plant are studied over a wide range.
PMCID: PMC2727369  PMID: 19495717
Oxyfuel; Emissions; CO2; Carbon capture
13.  Cost-effectiveness of laser Doppler imaging in burn care in the Netherlands 
BMC Surgery  2013;13:2.
Early accurate assessment of burn depth is important to determine the optimal treatment of burns. The method most used to determine burn depth is clinical assessment, which is the least expensive, but not the most accurate.
Laser Doppler imaging (LDI) is a technique with which a more accurate (>95%) estimate of burn depth can be made by measuring the dermal perfusion. The actual effect on therapeutic decisions, clinical outcomes and the costs of the introduction of this device, however, are unknown. Before we decide to implement LDI in Dutch burn care, a study on the effectiveness and cost-effectiveness of LDI is necessary.
A multicenter randomised controlled trial will be conducted in the Dutch burn centres: Beverwijk, Groningen and Rotterdam. All patients treated as outpatient or admitted to a burn centre within 5 days post burn, with burns of indeterminate depth (burns not obviously superficial or full thickness) and a total body surface area burned of ≤ 20% are eligible. A total of 200 patients will be included. Burn depth will be diagnosed by both clinical assessment and laser Doppler imaging between 2–5 days post burn in all patients. Subsequently, patients are randomly divided in two groups: ‘new diagnostic strategy’ versus ‘current diagnostic strategy’. The results of the LDI-scan will only be provided to the treating clinician in the ‘new diagnostic strategy’ group. The main endpoint is the effect of LDI on wound healing time.
In addition we measure: a) the effect of LDI on other patient outcomes (quality of life, scar quality), b) the effect of LDI on diagnostic and therapeutic decisions, and c) the effect of LDI on total (medical and non-medical) costs and cost-effectiveness.
This trial will contribute to our current knowledge on the use of LDI in burn care and will provide evidence on its cost-effectiveness.
Trial registration
PMCID: PMC3574826  PMID: 23369360
Laser doppler imaging; Burns; Diagnosis; Cost-effectiveness analysis
As this paper goes to press a complete review of the chemistry of the fertile egg will be appearing (19). The author, Mr. J. Needham, was kind enough to allow me to inspect his manuscript and thus avail myself of the comprehensive bibliography and discussion. It is surprising that no biochemists have estimated the changing water content of the egg during incubation. Many of the analyses reported in Needham's review were expressed in per cent of total weight or per cent of dry solid, and consequently are of questionable value, since these latter functions are themselves changing; the former due to water evaporation and the latter through the addition of shell constituents and the burning of oxidizable organic compounds. Moreover, there has been no statistical treatment of the results, and the reliability of the average, figures obtained has consequently been difficult to estimate. Tangl's work, quoted throughout this paper, except for its lack of statistical treatment is more enlightening. However, his concept of the so called "Energy of Embryogenesis" which he propounds, seems to me misleading and unwarranted. What Tangl measured was the amount and the caloric value of the solid material burned and thus the quantity of energy lost during the embryonic period. The latter is equivalent to the usual measurements of catabolism. In the case of the embryo it is not basal metabolism which is being estimated, since the conditions are not basal. The embryo is absorbing and assimilating nutriment all the while at a relatively rapid rate. The calorific value of the oxidized solid, which is in truth the amount of energy lost during a certain chosen interval, in Tangl's judgment stands for the energy of embryogenesis; i.e., the energy of development (growth + differentiation). We believe that this conception is erroneous. The two processes, anabolism and catabolism, occur together and undoubtedly have some relationship, but surely one is not a measure of the other. In a starving animal, and so probably in a starving embryo, there is a considerable amount of so called basal metabolism. Thus if the "Embryogenetic Energy" were measured under these conditions a figure would be obtained for which there was no growth to correspond, or in other words there would be a value for something which did not exist. It will be seen in our later communications that the changes with age of metabolic rate and growth rate do not coincide. The amount of catabolism under certain circumstances does not accelerate growth or anabolism, but seems rather to be a limiting factor. It is as if when the absorbed energy were constant an increase of catabolism would make inroads upon the amount of energy which otherwise would remain for storage (growth). If, as Pembrey's (20) experiments would tend to show, there is an increase of metabolism in the oldest embryos when the outside temperature is lowered, one would find at the end of incubation in such cases that there was a greater amount of so called "Energy of Development" but smaller embryo. It seems that the potential energy amassed as growth comes from that remaining after the needs of the body have been satisfied. The results of the experiments described in this paper have formed the basis for judgment in the selection of suitable standard conditions for the incubation of hen's eggs. Standardization was necessary so that in future experiments the more important environmental factors might be kept uniform within a certain appropriate range and therefore not be held accountable for deviations observed in the embryos. Henceforth in this series of papers the term "standard incubation conditions" will signify that (1) the temperature was constantly at 38.8 ± 0.4°C., (2) the humidity at 67.5 ± 2.5 per cent, (3) there was a continuous flow of warm air into the incubator to provide the necessary circulation, and (4) the eggs were rolled once a day within the constant temperature room. The incubator, a double-walled copper cabinet, stands in a constant temperature room, the fluctuations of which are ± 1.0°C. The space between the walls of the incubator is filled with water which serves as a buffer to outer variations. It might be repeated that all the eggs are from White Leghorn hens, are incubated 2 days after laying, and that they are kept cold during the interval necessary for transportation. With the figures from our chemical analyses and metabolic rate experiments, it was possible to calculate values for the concentration of total solids, fat, and nitrogen throughout the incubation period. These data were necessary as a general chemical background for further work. The results of the calculations are obviously rough. Because of the great variability of the eggs a satisfactory degree of accuracy could not have been attained without a very large number of analyses supplemented by complete statistical treatment. The necessity for such a comprehensive study was not evident, and it is our belief that the approximations reached in this paper are sufficiently close to serve our present purposes. The chief facts that have been ascertained in this investigation are (1) Loss of water by the egg during incubation is a function of the atmospheric humidity in its immediate environment. More rapid circulation of air lowers the humidity around the egg and thus increases evaporation. Other facts influencing evaporation are (a) atmospheric temperature, (b) thickness and surface area of the shell, and (c) conditions within the egg, the most important of which, it is suggested, is the amount of heat produced by the embryo. The latter factor, in turn, depends upon its size and age, and a significant change does not become apparent until the last 3 or 4 days of incubation, that is to say, when the embryo is of sufficient mass to exert a measurable force. (2) The surface area of the eggs in sq. cm. may be approximately represented by the formula S = K W⅔, where K = 5.07 ± 0.10, and W = the weight of the whole egg in gm. (3) There is a loss of weight by the shell during incubation. This is most noticeable near the end of the cycle, when the loss seems to parallel in general the weight of the embryo. (4) There is also a loss of solid matter during incubation. Chemical analyses indicate that about 98 per cent of the material oxidized is fat. This conclusion is corroborative of previous work by Hasselbalch, Hasselbalch and Bohr, and Tangl. (5) Carbon dioxide may be measured with relative accuracy. When it is assumed that it is derived from the oxidation of fat, satisfactory corroboration of the chemical analyses is obtained. These experiments have furnished the data from which the values have been calculated for total solids, fats, and protein in the whole egg throughout incubation. The figures may be used later for comparison with the concentration of these substances within the embryo.
PMCID: PMC2140783  PMID: 19872226
15.  A comprehensive experimental and detailed chemical kinetic modelling study of 2,5-dimethylfuran pyrolysis and oxidation 
Combustion and flame  2013;160(11):2291-2318.
The pyrolytic and oxidative behaviour of the biofuel 2,5-dimethylfuran (25DMF) has been studied in a range of experimental facilities in order to investigate the relatively unexplored combustion chemistry of the title species and to provide combustor relevant experimental data. The pyrolysis of 25DMF has been re-investigated in a shock tube using the single-pulse method for mixtures of 3% 25DMF in argon, at temperatures from 1200–1350 K, pressures from 2–2.5 atm and residence times of approximately 2 ms.
Ignition delay times for mixtures of 0.75% 25DMF in argon have been measured at atmospheric pressure, temperatures of 1350–1800 K at equivalence ratios (ϕ) of 0.5, 1.0 and 2.0 along with auto-ignition measurements for stoichiometric fuel in air mixtures of 25DMF at 20 and 80 bar, from 820–1210 K.
This is supplemented with an oxidative speciation study of 25DMF in a jet-stirred reactor (JSR) from 770–1220 K, at 10.0 atm, residence times of 0.7 s and at ϕ = 0.5, 1.0 and 2.0.
Laminar burning velocities for 25DMF-air mixtures have been measured using the heat-flux method at unburnt gas temperatures of 298 and 358 K, at atmospheric pressure from ϕ = 0.6–1.6. These laminar burning velocity measurements highlight inconsistencies in the current literature data and provide a validation target for kinetic mechanisms.
A detailed chemical kinetic mechanism containing 2768 reactions and 545 species has been simultaneously developed to describe the combustion of 25DMF under the experimental conditions described above. Numerical modelling results based on the mechanism can accurately reproduce the majority of experimental data. At high temperatures, a hydrogen atom transfer reaction is found to be the dominant unimolecular decomposition pathway of 25DMF. The reactions of hydrogen atom with the fuel are also found to be important in predicting pyrolysis and ignition delay time experiments.
Numerous proposals are made on the mechanism and kinetics of the previously unexplored intermediate temperature combustion pathways of 25DMF. Hydroxyl radical addition to the furan ring is highlighted as an important fuel consuming reaction, leading to the formation of methyl vinyl ketone and acetyl radical. The chemically activated recombination of HȮ2 or CH3Ȯ2 with the 5-methyl-2-furanylmethyl radical, forming a 5-methyl-2-furylmethanoxy radical and ȮH or CH3Ȯ radical is also found to exhibit significant control over ignition delay times, as well as being important reactions in the prediction of species profiles in a JSR. Kinetics for the abstraction of a hydrogen atom from the alkyl side-chain of the fuel by molecular oxygen and HȮ2 radical are found to be sensitive in the estimation of ignition delay times for fuel-air mixtures from temperatures of 820–1200 K.
At intermediate temperatures, the resonantly stabilised 5-methyl-2-furanylmethyl radical is found to predominantly undergo bimolecular reactions, and as a result sub-mechanisms for 5-methyl-2-formylfuran and 5-methyl-2-ethylfuran, and their derivatives, have also been developed with consumption pathways proposed. This study is the first to attempt to simulate the combustion of these species in any detail, although future refinements are likely necessary.
The current study illustrates both quantitatively and qualitatively the complex chemical behavior of what is a high potential biofuel. Whilst the current work is the most comprehensive study on the oxidation of 25DMF in the literature to date, the mechanism cannot accurately reproduce laminar burning velocity measurements over a suitable range of unburnt gas temperatures, pressures and equivalence ratios, although discrepancies in the experimental literature data are highlighted. Resolving this issue should remain a focus of future work.
PMCID: PMC3837218  PMID: 24273333
16.  Effects of a Circulating-water Garment and Forced-air Warming on Body Heat Content and Core Temperature 
Anesthesiology  2004;100(5):1058-1064.
Background: Forced-air warming is sometimes unable to maintain perioperative normothermia. We therefore compared heat transfer, regional heat distribution, and core rewarming of forced-air warming with a novel circulating-water garment.
Methods: Nine volunteers were each evaluated on two randomly ordered study days. They were anesthetized and cooled to a core temperature near 34°C. The volunteers were subsequently warmed for 2.5 hours with either a circulating-water garment or forced-air cover. Overall, heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Average arm and leg (peripheral) tissue temperatures were determined from 18 intramuscular needle thermocouples, 15 skin thermal flux transducers, and “deep” arm and foot thermometers.
Results: Heat production (≈ 60 kcal/h) and loss (≈45 kcal/h) were similar with each treatment before warming. The increase in heat transfer across anterior portions of the skin surface was similar with each warming system (≈65 kcal/h). Forced-air warming had no effect on posterior heat transfer whereas circulating-water transferred 21 ± 9 kcal/h through the posterior skin surface after a half hour of warming. Over 2.5 h, circulating-water thus increased body heat content 56% more than forced air. Core temperatures thus increased faster than with circulating water than forced air, especially during the first hour, with the result that core temperature was 1.1 ± 0.7°C greater after 2.5 h (P < 0.001). Peripheral tissue heat content increased twice as much as core heat content with each device, but the core-to-peripheral tissue temperature gradient remained positive throughout the study.
Conclusions: The circulating-water system transferred more heat than forced air, with the difference resulting largely from posterior heating. Circulating water rewarmed patients 0.4°C/h faster than forced air. A substantial peripheral-to-core tissue-temperature gradient with each device indicated that peripheral tissues insulated the core, thus slowing heat transfer.
PMCID: PMC1409744  PMID: 15114200
17.  Burns From Hot Wheat Bags: A Public Safety Issue 
Eplasty  2011;11:e36.
Introduction: Wheat bags are therapeutic devices that are heated in microwaves and commonly used to provide relief from muscle and joint pain. The Royal Adelaide Hospital Burns Unit has observed a number of patients with significant burn injuries resulting from their use. Despite their dangers, the products come with limited safety information. Methods: Data were collected from the Burns Unit database for all patients admitted with burns due to hot wheat bags from 2004 to 2009. This was analyzed to determine the severity of the burn injury and identify any predisposing factors. An experimental study was performed to measure the temperature of wheat bags when heated to determine their potential for causing thermal injury. Results: 11 patients were admitted with burns due to hot wheat bags. The median age was 52 years and the mean total body surface area was 1.1%. All burns were either deep dermal (45.5%) or full thickness (54.5%). Ten patients required operative management. Predisposing factors (eg, neuropathy) to thermal injury were identified in 7 patients. The experimental study showed that hot wheat bags reached temperatures of 57.3°C (135.1°F) when heated according to instructions, 63.3°C (145.9°F) in a 1000 W microwave and 69.6°C (157.3°F) on reheating. Conclusions: Hot wheat bags cause serious burn injury. When heated improperly, they can reach temperatures high enough to cause epidermal necrosis in a short period of time. Patients with impaired temperature sensation are particularly at risk. There should be greater public awareness of the dangers of wheat bag use and more specific safety warnings on the products.
PMCID: PMC3160380  PMID: 21915357
18.  Quantitation of Pseudomonas aeruginosa in wound biopsy samples: from bacterial culture to rapid `real-time' polymerase chain reaction 
Critical Care  2000;4(4):255-262.
We developed a real-time detection (RTD) polymerase chain reaction (PCR) with rapid thermal cycling to detect and quantify Pseudomonas aeruginosa in wound biopsy samples. This method produced a linear quantitative detection range of 7 logs, with a lower detection limit of 103 colony-forming units (CFU)/g tissue or a few copies per reaction. The time from sample collection to result was less than 1h. RTD-PCR has potential for rapid quantitative detection of pathogens in critical care patients, enabling early and individualized treatment.
Early diagnosis of wound colonisation or prediction of wound sepsis provides an opportunity for therapeutic intervention. There is need for qualitative and quantitative tests that are more rapid than bacterial culture. Pseudomonas aeruginosa results in high morbidity and mortality rates, is inherently resistant to common antibiotics, and is increasingly being isolated as a nosocomial pathogen. We developed three PCR-based methods to detect and quantify P aeruginosa in wound biopsy samples: conventional PCR, enzyme-linked immunosorbent assay (ELISA)-PCR, and RTD-PCR with rapid thermal cycling (LightCycler™ technology), all based on the amplification of the outer membrane lipoprotein gene oprL. We compared the efficacy of these methods to bacterial culture by quantitatively measuring levels of P aeruginosa in serial dilutions, in reconstituted skin samples and 21 burn wound biopsy samples.
Materials and methods:
Serial 10-fold dilutions were made from an overnight P aeruginosa culture and plated out onto Luria-Bertani and cetrimide agar plates. The agar plates were incubated overnight at 37°C, and the colonies were counted in order to estimate the number of CFU per dilution tube. A sample was taken from each dilution tube as a template for the three PCR-based methods.
Serial P aeruginosa dilutions (see above) were added to uninfected cadaveric skin. The reconstituted biopsy samples were homogenized using a tissue tearer and DNA was extracted using XTRAX DNA buffer. The DNA was resuspended in distilled water. A sample was taken as a template for the PCR-based methods.
Twenty-one burn wound biopsy samples were taken from nine patients with suspected P aeruginosa burn wound infection. The biopsy samples were longitudinally divided into two pieces. From one piece, DNA was extracted (using XTRAX DNA buffer) and used as a template for PCR-based techniques (see above). The other piece was homogenized, in physiological water, using a tissue tearer. Serial 10-fold dilutions of the suspension were spread on Luria-Bertani and cetrimide agar plates. Colony counts were performed after overnight incubation at 37°C.
The PCR mixture contained sterile distilled water, PCR buffer, deoxynucleotide mixture or digoxigenin labelling mix, MgCl2, diluted template, primers PAL1 and PAL2, and AmpliTaQ DNA polymerase. The amplification was performed in a GeneAmp® PCR System 2400. An aliquot of the reaction mixture was put on an agarose gel for electrophoresis and visualisation of the PCR product. An image of the gel was made using a digital camera. Image analysis software was used to calculate the band mass of the experimental bands.
An aliquot of the digoxigenin labelling reaction was denatured and then hybridized with the biotinylated capture probe PrL. Some of the resultant solution was transferred to a well of a streptavidin-coated microtitre plate (MTP) and incubated for 3 h at 45°C. The solution was discarded. Peroxidase conjugated antidigoxigenin was added and the MTP was incubated for 30 min at 37°C. The solution was discarded and ABTS substrate was added. The MTP was incubated for 30 min at 37°C. Absorbance was read at 405 nm.
The RTD-PCR mixture contained PCR grade sterile water, diluted template DNA, primers PAL1 and PAL2, 3' fluorescein (FL)-labelled probe oprL-FL, 5' LC Red 640-labelled and 3' phosphorylated probe oprL-LC, MgCl2, and LC DNA Master Hybridisation Probes, containing Taq DNA polymerase, reaction buffer, dNTP mix with dUTP instead of dTTP, and MgCl2. The amplification was performed in a LightCycler™. The fluorescence signal of LC Red 640 was measured during the annealing phase. The measured fluorescence data was processed with analysis software.
Results and discussion:
The three methods showed a good concordance with the culture results. Conventional PCR was at least 100 times less sensitive than bacterial culture and had a low dynamic range (2 logs). With a lower detection limit of 103 CFU/g tissue, ELISA-PCR was ten times more sensitive than conventional PCR. The dynamic range, however, did not increase. ELISA-PCR is very time consuming (8 h). The RTD-PCR produced a linear quantitative detection range of 7 logs with a lower detection limit of 103 CFU/g tissue. More important, however, was that the time from sample collection to result was less than 1 h. Two biopsy specimens scored significantly higher in ELISA-PCR and RTD-PCR than in bacterial culture. This could indicate that DNA from dead bacteria was amplified. One out of ten culture positive biopsy samples was found negative by all PCR-based methods. Topical antimicrobial agents possibly inhibited PCR. These results show that RTD-PCR has potential for the rapid quantitative detection of pathogens in critical care patients, enabling early and individualized treatment. Further study is required to assess the reliability of this new technology, and its impact on patient outcome and hospital costs.
PMCID: PMC29046  PMID: 11056755
burn wound; polymerase chain reaction; Pseudomonas aeruginosa; quantitation; sepsis
19.  Self-Paced Exercise Performance in the Heat After Pre-Exercise Cold-Fluid Ingestion 
Journal of Athletic Training  2011;46(6):592-599.
Precooling is the pre-exercise reduction of body temperature and is an effective method of improving physiologic function and exercise performance in environmental heat. A practical and effective method of precooling suitable for application at athletic venues has not been demonstrated.
To confirm the effectiveness of pre-exercise ingestion of cold fluid without fluid ingestion during exercise on pre-exercise core temperature and to determine whether pre-exercise ingestion of cold fluid alone without continued provision of cold fluid during exercise can improve exercise performance in the heat.
Randomized controlled clinical trial.
Environmental chamber at an exercise physiology laboratory that was maintained at 32°C, 60% relative humidity, and 3.2 m/s facing air velocity.
Patients or Other Participants:
Seven male recreational cyclists (age = 21 ± 1.5 years, height = 1.81 ± 0.07 m, mass = 78.4 ± 9.2 kg) participated.
Participants ingested 900 mL of cold (2°C) or control (37°C) flavored water in 3 300-mL aliquots over 35 minutes of pre-exercise rest.
Main Outcome Measure(s):
Rectal temperature and thermal comfort before exercise and distance cycled, power output, pacing, rectal temperature, mean skin temperature, heart rate, blood lactate, thermal comfort, perceived exertion, and sweat loss during exercise.
During rest, a greater decrease in rectal temperature was observed with ingestion of the cold fluid (0.41 ± 0.16°C) than the control fluid (0.17 ± 0.17°C) over 35 to 5 minutes before exercise (t6 = −3.47, P = .01). During exercise, rectal temperature was lower after ingestion of the cold fluid at 5 to 25 minutes (t6 range, 2.53–3.38, P ≤ .05). Distance cycled was greater after ingestion of the cold fluid (19.26 ± 2.91 km) than after ingestion of the control fluid (18.72 ± 2.59 km; t6 = −2.80, P = .03). Mean power output also was greater after ingestion of the cold fluid (275 ± 27 W) than the control fluid (261 ± 22 W; t6 = −2.13, P = .05). No differences were observed for pacing, mean skin temperature, heart rate, blood lactate, thermal comfort, perceived exertion, and sweat loss (P > .05).
We demonstrated that pre-exercise ingestion of cold fluid is a simple, effective precooling method suitable for field-based application.
PMCID: PMC3418935  PMID: 22488183
precooling; hyperthermia; time trial
20.  Heat exhaustion in a deep underground metalliferous mine 
OBJECTIVES—To examine the incidence, clinical state, personal risk factors, haematology, and biochemistry of heat exhaustion occurring at a deep underground metalliferous mine. To describe the underground thermal conditions associated with the occurrence of heat exhaustion.
METHODS—A 1 year prospective case series of acute heat exhaustion was undertaken. A history was obtained with a structured questionnaire. Pulse rate, blood pressure, tympanic temperature, and specific gravity of urine were measured before treatment. Venous blood was analysed for haematological and biochemical variables, during the acute presentation and after recovery. Body mass index (BMI) and maximum O2 consumption (V̇O2 max) were measured after recovery. Psychrometric wet bulb temperature, dry bulb temperature, and air velocity were measured at the underground sites where heat exhaustion had occurred. Air cooling power and psychrometric wet bulb globe temperature were derived from these data.
RESULTS—106 Cases were studied. The incidence of heat exhaustion during the year was 43.0 cases / million man-hours. In February it was 147 cases / million man-hours. The incidence rate ratio for mines operating below 1200 m compared with those operating above 1200 m was 3.17. Mean estimated fluid intake was 0.64 l/h (SD 0.29, range 0.08-1.50). The following data were increased in acute presentation compared with recovery (p value, % of acute cases above the normal clinical range): neutrophils (p<0.001, 36%), anion gap (p<0.001, 63%), urea (p<0.001, 21%), creatinine (p<0.001, 30%), glucose (p<0.001, 15%), serum osmolality (p=0.030, 71%), creatine kinase (p=0.002, 45%), aspartate transaminase (p<0.001, 14%), lactate dehydrogenase (p<0.001, 9.5%), and ferritin (p<0.001, 26%). The following data were depressed in acute presentation compared with recovery (p value, % of acute cases below the normal clinical range): eosinophils (p=0.003, 38%) and bicarbonate (p=0.011, 32%). Urea and creatinine were significantly increased in miners with heat cramps compared with miners without this symptom (p<0.001), but there was no significant difference in sodium concentration (p=0.384). Mean psychrometric wet bulb temperature was 29.0°C (SD 2.2, range 21.0-34.0). Mean dry bulb temperature was 37.4°C (SD 2.4, range 31.0-43.0). Mean air velocity was 0.54 m/s (SD 0.57, range 0.00-4.00). Mean air cooling power was 148 W/m2 (SD 49, range 33-290) Mean psychrometric wet bulb globe temperature was 31.5°C (SD 2.0, range 25.2-35.3). Few cases (<5%) occurred at psychrometric wet bulb temperature <25.0°C, dry bulb temperature <33.8°C, air velocity >1.56 m/s, air cooling power >248 W/m2, or psychrometric wet bulb globe temperature <28.5°C.
CONCLUSION—Heat exhaustion in underground miners is associated with dehydration, neutrophil leukocytosis, eosinopenia, metabolic acidosis, increased glucose and ferritin, and a mild rise in creatine kinase, aspartate transaminase, and lactate dehydrogenase. Heat cramps are associated with dehydration but not hyponatraemia. The incidence of heat exhaustion increases during summer and at depth. An increased fluid intake is required. Heat exhaustion would be unlikely to occur if ventilation and refrigeration achieved air cooling power >250 W/m2 at all underground work sites.

Keywords: heat; mining; ventilation
PMCID: PMC1739920  PMID: 10810098
21.  Rewarming preterm infants on a heated, water filled mattress. 
Archives of Disease in Childhood  1989;64(5):687-692.
Sixty low birthweight infants (1000-2000 g) admitted to a neonatal care unit in Turkey were studied. Those not requiring intensive care were randomly assigned for treatment either in a cot on a heated, water filled mattress kept at 37 degrees C (n = 28) or in air heated incubators with a mean air temperature of 35 degrees C (n = 32). On admission 53 (88.3%) of the infants had body temperatures between 30 degrees and 36 degrees C. There was good correlation between axillary and rectal temperatures in the infants while they were hypothermic. Normal temperatures were achieved within the first day and remained within this range during the subsequent days after admission in all the infants treated on the heated, water filled mattress, whereas they were not achieved until three days later in the incubator group. The neonatal mortality among those treated on the heated, water filled mattress was 21%, and among those treated in the incubator 34%. The heated, water filled mattress provides a good alternative to skin to skin contact with the mother, and to the use of a complex and expensive incubator for rapidly attaining and maintaining normal temperatures in the low birthweight newborn.
PMCID: PMC1792015  PMID: 2730122
22.  Is Oral Temperature an Accurate Measurement of Deep Body Temperature? A Systematic Review 
Journal of Athletic Training  2011;46(5):566-573.
Oral temperature might not be a valid method to assess core body temperature. However, many clinicians, including athletic trainers, use it rather than criterion standard methods, such as rectal thermometry.
To critically evaluate original research addressing the validity of using oral temperature as a measurement of core body temperature during periods of rest and changing core temperature.
Data Sources:
In July 2010, we searched the electronic databases PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), SPORTDiscus, Academic Search Premier, and the Cochrane Library for the following concepts: core body temperature, oral, and thermometers. Controlled vocabulary was used, when available, as well as key words and variations of those key words. The search was limited to articles focusing on temperature readings and studies involving human participants.
Data Synthesis:
Original research was reviewed using the Physiotherapy Evidence Database (PEDro). Sixteen studies met the inclusion criteria and subsequently were evaluated by 2 independent reviewers. All 16 were included in the review because they met the minimal PEDro score of 4 points (of 10 possible points), with all but 2 scoring 5 points. A critical review of these studies indicated a disparity between oral and criterion standard temperature methods (eg, rectal and esophageal) specifically as the temperature increased. The difference was −0.50°C ± 0.31°C at rest and −0.58°C ± 0.75°C during a nonsteady state.
Evidence suggests that, regardless of whether the assessment is recorded at rest or during periods of changing core temperature, oral temperature is an unsuitable diagnostic tool for determining body temperature because many measures demonstrated differences greater than the predetermined validity threshold of 0.27°C (0.5°F). In addition, the differences were greatest at the highest rectal temperatures. Oral temperature cannot accurately reflect core body temperature, probably because it is influenced by factors such as ambient air temperature, probe placement, and ingestion of fluids. Any reliance on oral temperature in an emergency, such as exertional heat stroke, might grossly underestimate temperature and delay proper diagnosis and treatment.
PMCID: PMC3418963  PMID: 22488144
exertional heat stroke; hyperthermia; core temperature
23.  Patients’ experiences of cold exposure during ambulance care 
Exposure to cold temperatures is often a neglected problem in prehospital care. Cold exposure increase thermal discomfort and, if untreated causes disturbances of vital body functions until ultimately reaching hypothermia. It may also impair cognitive function, increase pain and contribute to fear and an overall sense of dissatisfaction. The aim of this study was to investigate injured and ill patients’ experiences of cold exposure and to identify related factors.
During January to March 2011, 62 consecutively selected patients were observed when they were cared for by ambulance nursing staff in prehospital care in the north of Sweden. The field study was based on observations, questions about thermal discomfort and temperature measurements (mattress air and patients’ finger temperature). Based on the observation protocol the participants were divided into two groups, one group that stated it was cold in the patient compartment in the ambulance and another group that did not. Continuous variables were analyzed with independent sample t-test, paired sample t-test and dichotomous variables with cross tabulation.
In the ambulance 85% of the patients had a finger temperature below comfort zone and 44% experienced the ambient temperature in the patient compartment in the ambulance to be cold. There was a significant decrease in finger temperature from the first measurement indoor compared to measurement in the ambulance. The mattress temperature at the ambulance ranged from −22.3°C to 8.4°C.
Cold exposure in winter time is common in prehospital care. Sick and injured patients immediately react to cold exposure with decreasing finger temperature and experience of discomfort from cold. Keeping the patient in the comfort zone is of great importance. Further studies are needed to increase knowledge which can be a base for implications in prehospital care for patients who probably already suffer for other reasons.
PMCID: PMC3693912  PMID: 23742143
Cold exposure; Comfort zone; Finger temperature; Thermal comfort; Thermal discomfort; Patients’ experience
24.  Stress-Mediated Increases in Systemic and Local Epinephrine Impair Skin Wound Healing: Potential New Indication for Beta Blockers 
PLoS Medicine  2009;6(1):e1000012.
Stress, both acute and chronic, can impair cutaneous wound repair, which has previously been mechanistically ascribed to stress-induced elevations of cortisol. Here we aimed to examine an alternate explanation that the stress-induced hormone epinephrine directly impairs keratinocyte motility and wound re-epithelialization. Burn wounds are examined as a prototype of a high-stress, high-epinephrine, wound environment. Because keratinocytes express the β2-adrenergic receptor (β2AR), another study objective was to determine whether β2AR antagonists could block epinephrine effects on healing and improve wound repair.
Methods and Findings
Migratory rates of normal human keratinocytes exposed to physiologically relevant levels of epinephrine were measured. To determine the role of the receptor, keratinocytes derived from animals in which the β2AR had been genetically deleted were similarly examined. The rate of healing of burn wounds generated in excised human skin in high and low epinephrine environments was measured. We utilized an in vivo burn wound model in animals with implanted pumps to deliver β2AR active drugs to study how these alter healing in vivo. Immunocytochemistry and immunoblotting were used to examine the up-regulation of catecholamine synthetic enzymes in burned tissue, and immunoassay for epinephrine determined the levels of this catecholamine in affected tissue and in the circulation. When epinephrine levels in the culture medium are elevated to the range found in burn-stressed animals, the migratory rate of both cultured human and murine keratinocytes is impaired (reduced by 76%, 95% confidence interval [CI] 56%–95% in humans, p < 0.001, and by 36%, 95% CI 24%–49% in mice, p = 0.001), and wound re-epithelialization in explanted burned human skin is delayed (by 23%, 95% CI 10%–36%, p = 0.001), as compared to cells or tissues incubated in medium without added epinephrine. This impairment is reversed by β2AR antagonists, is absent in murine keratinocytes that are genetically depleted of the β2AR, and is reproduced by incubation of keratinocytes with other β2AR-specific agonists. Activation of the β2AR in cultured keratinocytes signals the down-regulation of the AKT pathway, accompanied by a stabilization of the actin cytoskeleton and an increase in focal adhesion formation, resulting in a nonmigratory phenotype. Burn wound injury in excised human skin also rapidly up-regulates the intra-epithelial expression of the epinephrine synthesizing enzyme phenylethanolamine-N-methyltransferase, and tissue levels of epinephrine rise dramatically (15-fold) in the burn wounded tissue (values of epinephrine expressed as pg/ug protein ± standard error of the mean: unburned control, 0.6 ± 0.36; immediately postburn, 9.6 ± 1.58; 2 h postburn, 3.1 ± 1.08; 24 h post-burn, 6.7 ± 0.94). Finally, using an animal burn wound model (20% body surface in mice), we found that systemic treatment with βAR antagonists results in a significant increase (44%, 95% CI 27%–61%, p < 0.00000001) in the rate of burn wound re-epithelialization.
This work demonstrates an alternate pathway by which stress can impair healing: by stress-induced elevation of epinephrine levels resulting in activation of the keratinocyte β2AR and the impairment of cell motility and wound re-epithelialization. Furthermore, since the burn wound locally generates epinephrine in response to wounding, epinephrine levels are locally, as well as systemically, elevated, and wound healing is impacted by these dual mechanisms. Treatment with beta adrenergic antagonists significantly improves the rate of burn wound re-epithelialization. This work suggests that specific β2AR antagonists may be apt, near-term translational therapeutic targets for enhancing burn wound healing, and may provide a novel, low-cost, safe approach to improving skin wound repair in the stressed individual.
Rivkah Isseroff and colleagues describe how stress-induced elevation of epinephrine levels can impair the healing of burns in mice and suggest that β2 adrenergic receptor antagonists may have a role in improving skin wound repair.
Editors' Summary
Skin—the largest organ in the human body—protects the rest of the body against infection by forming an impervious layer over the whole external body surface. Consequently, if this layer is damaged by rubbing, cutting, or burning, it must be quickly and efficiently repaired. Wound repair (healing) involves several different processes. First, the clotting cascade stops bleeding at the wound site and immune system cells attracted into the site remove any bacteria or debris in the wound. Various factors are released by the immune cells and the other cells in and near the damaged area that encourage the migration of several different sorts of cells into the wound. These cells proliferate and prepare the wound for “re-epithelialization.” In this process, keratinocytes (a type of epithelial cell that makes a tough, insoluble protein called keratin; epithelial cells cover all the surfaces of the body) migrate into the wound site and form a new, intact epithelial layer. If any of these processes fail, the result can be a chronic (long-lasting) nonhealing wound. In particular, if the wound does not re-epithelialize, it remains open and susceptible to infection and loss of body fluids.
Why Was This Study Done?
One factor that impairs the repair of skin wounds is stress. In stressful situations (including situations in which wounds are likely to occur), the human body releases several chemicals that prepare the body for “fight or flight,” including cortisol and epinephrine (also called adrenaline). Most scientists ascribe the effects of stress on wound healing to stress-induced increases in cortisol, but might stress-induced epinephrine also affect wound healing? In this study, the researchers test whether epinephrine impairs keratinocyte migration and re-epithelialization of burn wounds (keratinocytes have a receptor for epinephrine called the β2 adrenergic receptor [β2AR] on their cell surface that allows them to respond to epinephrine). They chose to study burn wounds for two reasons. First, major burns cause a massive release of stress chemicals into the bloodstream that raises blood levels (systemic levels) of cortisol and epinephrine for days or weeks after the initial trauma. Second, despite recent therapeutic advances, many people still die from major burns (4,000 every year in the USA alone) so there is a pressing need for better ways to treat this type of wound.
What Did the Researchers Do and Find?
The researchers investigated the effects of epinephrine on wound healing in three types of experiments. First, they looked at the effect of epinephrine on keratinocytes growing in dishes (in vitro experiments). Levels of epinephrine similar to those in the blood of stressed individuals greatly inhibited the motility and migration of human keratinocytes (isolated from the foreskin of newborn babies) and of mouse keratinocytes. It also inhibited the repair of scratch wounds made in monolayers of keratinocytes growing on dishes. Treatment of the cultures with a β2AR antagonist (a chemical that prevents epinephrine activating the β2AR) reversed the effects of epinephrine. In addition, the migration of mouse keratinocytes that had been genetically altered so that they did not express β2AR was not inhibited by epinephrine. Next, the researchers investigated the healing of burn wounds made in small pieces of human skin growing in dishes (ex vivo experiments). Burn injuries rapidly increased the amount of epinephrine in these tissue explants, they report, and treatment of the explants with a βAR antagonist (an inhibitor of all types of βARs) greatly increased wound re-epithelialization. Finally, the researchers report that the re-epithelialization of burn wounds in living mice was improved when the mice were treated with a β2AR antagonist.
What Do These Findings Mean?
These findings reveal a second pathway by which stress can impair wound healing. They show that stress-induced increases in systemic and local epinephrine activate β2ARs on keratinocytes and that this activation inhibits keratinocyte motility and wound re-epithelialization. Although results obtained in animals do not always reflect what happens in people, the finding that the treatment of mice with β2AR antagonists improves the rate of burn wound re-epithelialization, suggests that beta blockers—drugs that inhibit all βARs and that are widely used to treat high blood pressure and to prevent heart disease—or specific β2AR antagonists might provide a new therapeutic approach to the treatment of burns and, perhaps, chronic nonhealing wounds.
Additional Information.
Please access these Web sites via the online version of this summary at
Wikipedia has pages on wound healing, burn injuries, and epinephrine (Note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The MedlinePlus Encyclopedia has a page on burns (in English and Spanish)
MedlinePlus provides links to other information on burns (in English and Spanish)
PMCID: PMC2621262  PMID: 19143471
25.  Microdialysis shows metabolic effects in skin during fluid resuscitation in burn-injured patients 
Critical Care  2006;10(6):R172.
Established fluid treatment formulas for burn injuries have been challenged as studies have shown the presence of tissue hypoxia during standard resuscitation. Such findings suggest monitoring at the tissue level. This study was performed in patients with major burn injuries to evaluate the microdialysis technique for the continuous assessment of skin metabolic changes during fluid resuscitation and up to four days postburn.
We conducted an experimental study in patients with a burn injury, as represented by percentage of total body surface area burned (TBSA), of more than 25% in a university eight-bed burns intensive care unit serving about 3.5 million inhabitants. Six patients with a median TBSA percentage of 59% (range 33.5% to 90%) and nine healthy controls were examined by intracutaneous MD, in which recordings of glucose, pyruvate, lactate, glycerol, and urea were performed.
Blood glucose concentration peaked on day two at 9.8 mmol/l (6.8 to 14.0) (median and range) and gradually declined on days three and four, whereas skin glucose in MD continued to increase throughout the study period with maximum values on day four, 8.7 mmol/l (4.9 to 11.0). Controls had significantly lower skin glucose values compared with burn patients, 3.1 mmol/l (1.5 to 4.6) (p < 0.001). Lactate from burn patients was significantly higher than controls in both injured and uninjured skin (MD), 4.6 mmol/l (1.3 to 8.9) and 3.8 mmol/l (1.6 to 7.5), respectively (p < 0.01). The skin lactate/pyruvate ratio (MD) was significantly increased in burn patients on all days (p < 0.001). Skin glycerol (MD) was significantly increased at days three and four in burn patients compared with controls (p < 0.01).
Despite a strategy that fulfilled conventional goals for resuscitation, there were increased lactate/pyruvate ratios, indicative of local acidosis. A corresponding finding was not recorded systemically. We conclude that MD is a promising tool for depicting local metabolic processes that are not fully appreciated when examined systemically. Because the local response in glucose, lactate, and pyruvate metabolism seems to differ from that recorded systemically, this technique may offer a new method of monitoring organs.
PMCID: PMC1794489  PMID: 17166287

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