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PubMed1999

The combination of growth hormone with hepatocyte growth factor alters the acute phase response.

Recombinant human growth hormone (rhGH) and hepatocyte growth factor (HGF) have both been shown to individually modulate hepatic acute phase reactant proteins and cytokine expression following trauma through different pathways. Recombinant hGH has also been shown to decrease serum and hepatic HGF concentrations after a thermal injury. We hypothesized that the combination of rhGH plus HGF improves the burn-induced acute phase response. Fifty-six male Sprague-Dawley rats received a 60% TBSA third-degree scald burn and were randomly divided to receive either rhGH (2.5 mg/kg/day sc.) plus HGF (200 microg/kg i.v. every 12 h) or placebo (saline). Rats were sacrificed on post-burn days 1, 2, 5, or 7 and serum constitutive and acute phase proteins, TNF-alpha, IL-1beta, IL-6 and liver total protein measured. Hepatic cytokine gene expression, triglyceride concentration, and hepatocyte proliferation were also measured. In rats receiving rhGH/HGF, serum albumin increased on days 5 and 7 and transferrin on day 7 after burn compared to placebo (P<0.05). Haptoglobin decreased 5 days after burn compared to placebo (P<0.05). RhGH/HGF increased serum TNF-alpha on day 2 after burn, while it decreased serum IL-1beta on day 1 after burn compared with placebo (P<0.05). RhGH/HGF had no effect on hepatic cytokine gene expression compared with placebo. Liver total protein content and hepatocyte proliferation increased on days 1, 2, 5, and 7 after burn with rhGH/HGF treatment (P<0.05). These findings indicate that rhGH in combination with HGF exert additive effects on constitutive hepatic proteins and partial inhibitory effects on acute phase protein and cytokine expression. RhGH/HGF has a strong mitogenic effect on hepatocytes.

Acute-Phase Reaction↗
PubMed1999

Enhanced expression of neutrophil NADPH oxidase components in intestine of rats after burn injury.

We have evaluated the accumulation of neutrophils in the gut and their infiltration into the intestinal extravascular spaces in rats subjected to a 25% total body surface area scald burn. The accumulation of neutrophils was assessed via measurements of myeloperoxidase (MPO) activity in the intestinal homogenates, and the immunohistochemical localization of neutrophil NADPH oxidase component proteins (p47phox and p67phox) within the intestinal extravascular spaces determined neutrophil tissue infiltration. MPO measurements demonstrated a 12- and 21-fold increase above the control value in the intestinal tissue at day 1 and day 3 post-burn, respectively, suggesting that a substantial total tissue accumulation of neutrophils occurs in the gut after burn injury. The immunohistochemical staining procedures showed both a definitive presence of the neutrophil in the intestinal extravascular spaces and an enhanced immunoreactivity in neutrophils accumulating in intestine after burn injury. There was no evidence of either the presence of neutrophils in the extravascular regions or any significant neutrophil immunoreactivity to NADPH oxidase component proteins in the intestines of sham control rats. These findings indicate that burn injury causes an enhanced migration of circulating neutrophils into the intestinal interstitial spaces and an upregulation of NADPH oxidase activity in the infiltrating neutrophils.

Animals↗
PubMed2000

Does burn wound excision after thermal injury attenuate subsequent macrophage hyperactivity and immunosuppression?

Studies have shown that cell mediated immunity is suppressed markedly following thermal injury. Macrophages and the activation of an inflammatory cascade that includes interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNFalpha) and PGE2 have been implicated as causative factors. Burn wound excision and grafting is a common clinical practice that decreases patient morbidity and mortality. It is not known, however, if the salutary effects of this procedure are related to modulation of macrophage activity post-burn. Therefore, C57BL/6 female mice were subjected to a third-degree scald burn covering 25% of their total body surface area followed by complete excision and allografting of the injury site at 8, 24, or 72 h post-burn. Splenic macrophage function was assessed 7 days post-burn. Thermal injury without burn excision and grafting significantly increased macrophage TNFalpha, IL-6, nitric oxide, and PGE2 production in response to lipopolysaccharide stimulation, whereas IL-1beta production was not increased. Burn wound excision and grafting normalized TNFalpha production to sham levels, independent of when post-burn the procedure was conducted. In contrast, the elevated production of other inflammatory mediators (IL-1beta, IL-6, nitric oxide, PGE2) post-burn was unaffected by burn wound excision and grafting. Moreover, splenic T-lymphocyte proliferation was also suppressed at 7 days post-burn and was not improved by burn wound excision and grafting. These results, therefore, suggest that the beneficial effects of burn wound excision and grafting are likely to be related to the normalization of macrophage TNFalpha production as well as the maintenance of skin barrier function.

Animals↗
PubMed2001

Quantitative assessment of a circulating depolarizing factor in shock.

Sustained depolarization of cell membranes and cellular edema are known to accompany various forms of circulatory shock and probably contribute to hypovolemia and cellular dysfunction. It has been proposed that a circulating protein is responsible for these effects. In the present study we have confirmed the existence of a circulating depolarizing factor (CDF) in hemorrhagic shock, burn shock, sepsis, and cardiopulmonary bypass. Plasma samples from pigs or sheep in shock were quantitatively assayed for depolarizing activity using a microelectrode method on rat diaphragm in vitro. The depolarizing effect of CDF in vitro was similar in magnitude to that of shock in situ. We conclude that CDF can entirely account for membrane depolarization during shock. The depolarizing effect of CDF was dose-dependent and saturable; it could be reversed by rinsing the diaphragm with Ringer's or control plasma. CDF activity was detectable in plasma within 5 min after a severe scald and gradually increased over the next 25 min. Resuscitation of hemorrhaged pigs, but not burned sheep, eliminated plasma CDF activity.

Animals↗
PubMed2001

Gene expression in intestinal epithelial cells, IEC-6, is altered by burn injury-induced circulating factors.

Severe burn injury is commonly associated with significant changes in intestinal epithelial function. These changes include mucosal atrophy and increased permeability. To date, the mechanism by which burn injury alters intestinal epithelium function are not clear. We used an in vitro model of intestinal epithelium, IEC-6 cells, and observed that the integrity of confluent culture is disrupted and cell growth and migration rates are reduced in the presence of serum collected from scald burn injury rats (SRS) (6). To identify gene products involved in mechanisms underlying these effects, we used the cDNA expression microarray analysis and found that genes whose expression was affected by SRS in IEC-6 cells were primarily associated with cell shape, growth and death, stress-response, protein turnover and transport of water and electrolytes. These data demonstrate that a burn-induced circulating factor(s) modulates expression of genes, which may affect intestinal epithelial cell survival and function. Thus, these findings provide clues to the nature of molecular mechanisms potentially involved in multiple-organ malfunction, in particular the atrophy and enhanced permeability of gut mucosa, after burn injury.

Actins↗
PubMed2001

IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in no and hepatic NF-kappa B.

After a severe trauma, such as a cutaneous thermal injury, an increase in hepatocyte apoptosis has been associated with hepatocyte damage and impairment in hepatic function. Insulinlike growth factor-I (IGF-I) exerts antiapoptotic effects in several organs, thus improving organ homeostasis. The purpose of the present study was to determine whether IGF-I in combination with its principle binding protein-3 (BP-3) attenuates liver damage after a burn and whether this attenuation is through signals of the apoptotic-proliferative axis of hepatocytes. Sprague-Dawley rats (56 males) received a 60% total body surface area third-degree scald burn and were randomly divided to receive either rhlGF-I/BP3 (10 mg/kg/day s.c.) or saline (control). Serum aspartate transaminase (AST) and nitric oxide (NO), and hepatocyte proliferation and apoptosis, were measured on postburn days 1, 2, 5, and 7. Hepatic interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA and hepatic nuclear-factor kappa B (NF-kappa B) were determined at 1 and 2 days postburn. IGF-I/BP-3 decreased serum AST and increased serum NO at 1, 2, and 5 days after burn when compared with controls (P < 0.05). IGF-I/BP-3 increased hepatocyte proliferation on the first day after burn and decreased hepatocyte apoptosis at day 7 postburn when compared with controls (P < 0.05). IGF-I/BP-3 decreased hepatic IL-1 beta and TNF-alpha mRNA 1 day after burn (P < 0.05). IGF-I/BP-3 further increased hepatic NF-kappa B concentration 1 and 2 days postburn when compared with controls (P < 0.05). Recombinant hIGF-I in combination with its principle binding protein conserves hepatic homeostasis, which is associated with a transient increase in hepatocyte proliferation and decrease in hepatocyte apoptosis possibly through NO and hepatic NF-kappa B.

Animals↗
PubMed2001

Serum TGF-beta in thermally injured rats.

A severe thermal injury is commonly associated with immune suppression and increased susceptibility to sepsis, frequently leading to multiple organ failure. Transforming growth factor-beta (TGF-beta) is a potent immunosuppressive cytokine involved in complications associated with major trauma. Interleukin- 4 (IL-4) is thought to synergize the immunosuppressive activity of TGF-beta by promoting naive lymphocytes to differentiate and generate TGF-beta secreting cells. This study examines the alterations in serum levels of TGF-beta and IL-4 after a thermal injury. Male Sprague-Dawley rats (300-400 g) were anesthetized and received a 50% total body surface area full-thickness scald burn followed by fluid resuscitation and analgesia. Control rats were given the same treatment, but were immersed in water at room temperature. Rats were sacrificed from 1 h to 8 days after injury. Blood samples were collected aseptically from the inferior caval vein. Serum levels of TGF-beta and IL-4 were measured by enzyme linked immunosorbent assay. Rats in the control and thermal injury groups showed similar increases in serum TGF-beta 1 h after injury. A progressive increase in serum TGF-beta was observed in burned animals compared to control animals starting on day 3 and continued through day 8 (P < 0.01). Serum IL-4 levels in control and thermally injured animals remained undetectable (< 15.6 pg/mL) throughout the experiment. Thermal injury induces a significant increase in serum TGF-beta, which may contribute to post-burn immunosuppression with an increased susceptibility to sepsis.

Animals↗
PubMed2002

Gender differences in mortality following burn injury.

Clinical and experimental studies have demonstrated higher mortality following nonthermal trauma among males compared with females. To date, few clinical retrospective studies have focused on gender differences in outcome following burn injury with respect to age. All patients admitted to the University of Alabama at Birmingham (UAB) Burn Center between January 1994 and December 2000 were selected for inclusion in the study. Gender differences in demographic, clinical, and outcome characteristics were compared. Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between mortality and gender, both overall and stratified by age. Over the 7-year study period, 1229 males and 382 females were admitted to the UAB Burn Center, and mortality rates were 7.2% and 13.4%, respectively (P = 0.0002). Female patients were more likely to be older, of the black race, and in poorer health. In addition, females were more likely to suffer flame and scald burns. The association between mortality and gender was modified by age. Up to age 60, mortality rates among females were over twice that of males (OR 2.3, 95% Cl 1.4-3.8); however, no difference was noted among those 60 and older (OR 0.9, 95% Cl 0.5-1.6). These associations persisted following adjustment for potentially confounding variables. Causes and timing of death were similar for males and females. Women less than 60 years of age who sustain burn injuries have an increased risk of death compared with males. Differences in the natural history of nonthermal trauma and burn injury may provide insight regarding these divergent findings.

Adult↗
PubMed2002

Effect of bombesin on gut mucosal impairment after severe burn.

Severe cutaneous bum alters gut epithelial homeostasis. In previous studies, treatment with bombesin decreased mucosal atrophy and improved maintenance of gut mucosal integrity after severe burn. Our current hypothesis is that bombesin reduces burn-induced gut impairment by decreasing gut epithelial cell death. Fifty-four adult male Fisher-344 rats were randomly assigned to three groups: control, sham burn (I), burn (II), and burn + bombesin (III). Animals in groups II and III received a 60% total body surface area full thickness scald burn, and the treatment group (III) received bombesin subcutaneously (10 microg/kg, every 8 h) beginning immediately before the experiment. The proximal small bowel was harvested at 12 and 72 h after burn with measurement of wet and dry weight, mucosal weight, and protein content, and a 1-cm length of proximal end was excised and fixed in fomalin for histological and immunohistochemical observation. Data are expressed as means +/- SEM. Statistical analysis was by done by analysis of variance (significance at P < 0.05). Bombesin treatment attenuated mucosal atrophy demonstrated by restoration of the mucosal weight, mucosal protein content, and maintenance of mucosal height and total mucosal epithelial cell count. Gut epithelial cell apoptosis was, at least in part, inhibited by bombesin compared with a significant increase of gut cell apoptosis at 12 h after burn. Gut epithelial proliferation was not affected. Bombesin diminished burn-induced gut mucosal atrophy and gut epithelial cell apoptosis, suggesting that bombesin treatment may play an important role in the recovery of gut impairment after severe burn.

Animals↗
PubMed1989

Employment status and the frequency and causes of burn injuries in New England.

We analyzed a subset of data from the New England Regional Burn Program (NERBP) to assess the effects of employment status on the rates and causes of burn injuries in New England. The subset of the NERBP data analyzed pertained to residents of the six New England states who were hospitalized for the treatment of a burn injury sustained between July 1, 1978 and June 30, 1979 and who were aged 20 years or older at the time of the injury. Analysis of the data identified that men, particularly black men and young men, experienced higher burn rates than did their female, white, and older counterparts among both employed and unemployed persons. High burn rates were observed in Maine; low rates were observed in Rhode Island. Scalds were the most common type of burn among work-related burns to women and to men aged 20 to 54 years, and flame or flash burns were the most common otherwise. The majority of work-related burn injuries were caused by activities related to food preparation or consumption, motor vehicle repair and maintenance, and use of flammable liquids. Persons employed as operatives and laborers, or persons employed in the service occupations, appeared to have the highest risk of sustaining a burn injury while at work.

Accidents, Occupational↗
PubMedDate not supplied

The usefulness of computer-based instruction in providing educational opportunities for nursing staff.

Computer-based (CB) instruction offers an alternative method for healthcare facilities to provide in service training to the staff. The authors investigated CB instruction as a way to provide information on preventing suicide and depression, adverse medication events, foodborne illness, and burns and scalds to people who care for older adults. The study compared the effects of CB instruction with those of equivalent instructor-led (IL) workshops. Each group of learners significantly improved knowledge related to the topic presented. The CB and IL versions of the modules produced similar results. The participants enjoyed using the computers and found the program easy to use. The authors concluded that CB instruction can be an effective alternative method of providing educational opportunities and is a convenient and cost-effective way to provide those opportunities to nursing staff.

Adult↗
PubMed2003

Effect of acute ethanol exposure on the dermal inflammatory response after burn injury.

BACKGROUND: More than 100,000 people each year are admitted to U.S. hospitals for severe burn injury. Strikingly, ethanol use prior to injury is apparent in nearly 50% of burn patients, rendering them six times more likely to die from infection than patients not exposed to ethanol. We previously reported that the kinetics and magnitude of neutrophil chemokine production and subsequent accumulation of neutrophils in the lung was dramatically altered when ethanol exposure preceded injury. Here, we tested whether burn injury and ethanol exposure combined, altered susceptibility to infection, neutrophil chemoattractant production, and neutrophil accumulation at the site of the burn wound. METHODS: Male B(6)D(2)F1 mice were administered a dose of ethanol designed to achieve 90-100 mg/dl circulating levels and 30 min later subjected to a 15% total body surface area dorsal scald injury. Susceptibility to topically applied Pseudomonas aeruginosa was examined. At various times after injury, burn wound and normal tissues were collected for assessments of neutrophil counts, myeloperoxidase quantitation, and neutrophil chemoattractant (KC and MIP-2) production. RESULTS: Ethanol exposure prior to burn injury enhanced susceptibility to infection after burn and was associated with significantly elevated production of KC, but not MIP-2, at the wound site. Despite the enhanced elevation of KC, neutrophil accumulation in the wounds of ethanol exposed, burn injured mice did not differ from those that received burn injury alone. TNFalpha (a potent activator of neutrophils), however, was found to be significantly elevated in the wounds of mice that received only burn injury, but not in those that received injury in combination with prior ethanol exposure. CONCLUSION: In the presence of ethanol, neutrophils are adequately recruited to the site of burn injury, but their host defense functions are impaired, perhaps due to the lack of proinflammatory cytokines such as TNFalpha.

Animals↗
PubMedDate not supplied

The media glorifying burns: a hindrance to burn prevention.

The media have a profound influence on the actions of children and adults. Burns and burn prevention tend to be ignored or even mocked. The purpose of this presentation is to reveal the callousness of the media in its dealings with burns and burn prevention. Printed materials with a relationship to burns, risk of burning, or disrespect for the consequences of burns were collected. The materials were tabulated into four categories: comics, advertisements (ads), articles that made light of burns, and television shows that portrayed behavior that would risk burn injury. Most burn-related materials were found in comics or advertisements. Several comics made light of high-risk behavior with flames, scald injury, contact injury, or burns. In addition, several advertisements showed people on fire or actions that could easily lead to burns. Several articles and televisions shows portrayed high-risk behavior that, in some instances, led to copycat injuries. Flames are frequently used to sell items that target adolescent boys or young men. The high incidence injuries that frequent this population parallel the high-risk behaviors portrayed by the media. The media portrays flames and high-risk behavior for burn injury as being cool, funny, and without consequence. The use of flames on clothing and recreational equipment (skateboards, hot rods) particularly targets the high-risk adolescent male. The burn community should make the media aware of the harm it causes with its callous depiction and glorification of burns.

Accident Prevention↗
PubMedDate not supplied

Silver-sulfadiazine eschar pigmentation mimics invasive wound infection: a case report.

A 3-year-old girl with 52% TBSA scalds, mostly partial thickness, was treated topically with 5% mafenide acetate solution and 1% silver sulfadiazine cream. All blood cultures and wound swabs were negative for the first 5 days. On day 6 gram-negative bacteria and yeast forms were isolated from her wounds. High fever and leukocytosis were present and the child was treated with intravenous ampicillin and gentamicin according to sensitivity bacteriogram. The bacteria were identified as Pseudomonas aeruginosa and the yeast was Candida tropicalis. On day 7, Escherichia coli was identified in blood cultures and intravenous cefixime was added. Amphotericin B was added on day 9 when blood cultures grew Candida tropicalis and Burkholderia cepacia. On day 13 dark pigmentation foci developed on some areas of partial-thickness burns in the back, resembling invasive wound infection. White blood cell count was 14,300 cells/mm3, and her body temperature reached 39.7 degrees C. Cultures from the pigmented areas were negative, and biopsies revealed deposits of silver. Most of the areas healed uneventfully, and only about 8% TBSA needed grafting, including some of the pigmented areas. No residual pigmentation remained on discharge.

Anti-Infective Agents, Local↗
PubMedDate not supplied

Fusarium infections in burn patients: a case report and review of the literature.

Fusarium species, or saprophytic molds, are important plant pathogens and recognized as agents of human mycotic infections. Frequently superficial, deep-tissue involvement, and dissemination occurs in immunocompromised hosts with hematologic malignancies, aplastic anemia, and chemotherapy treatment. Presented in this work is a burn patient with a fatal disseminated infection in addition to a review of the literature. A 40-year-old white male acquired a 73% grease scald injury at work. His hospital course was interspersed with multiple episodes of Flavobacterium, Fusarium, Candida, Proteus, Enterococcus, coagulase-negative Staphylococcus, and Serratia infections. He underwent nine operative procedures for debridement, excision, and skin grafting. The last operative procedure included bilateral below knee amputations to halt an invasive Fusarium infection that was invading normal unburned skin. The patient died 55 days after injury. Fusarium and Aspergillus infections are frequently confused and do not have characteristic clinical features. With the prolonged survival of severely burned patients, better fungal diagnostic and treatment modalities are needed to improve outcome.

Adult↗
PubMedDate not supplied

Short-term propofol infusion as an adjunct to extubation in burned children.

Children who require intubation as a component of their burn management generally need heavy sedation, usually with a combination of opiate and benzodiazepine infusions with a target sensorium of light sleep. When extubation approaches, the need for sedation to prevent uncontrolled extubation can conflict with the desire to lighten sedation enough to ensure that airway protective reflexes are strong. The several hours' half-life of these medications can make this period of weaning challenging. Therefore, the hours preceding extubation are among the most difficult in which to ensure safe adequate sedation. The pharmacokinetics of propofol allow for the rapid emergence of a patient from deep sedation. We have had success with an extubation strategy using short-term propofol infusions in critically ill children. In this work, children were maintained on morphine and midazolam infusions per our unit protocol, escalating doses as required to maintain comfort. Approximately 8 hours before planned extubation, these infusions were decreased by approximately half and propofol infusion added to maintain a state of light sleep. Extubation was planned approximately 8 hours later to allow ample time for the chronically infused opiates and benzodiazepines to be metabolized down to the new steady-state level. Thirty minutes before planned extubation, propofol was stopped while morphine and midazolam infusions were maintained at the reduced level. When the children awakened from the propofol-induced state of light sleep, they were extubated while the reduced infusions of morphine and midazolam were maintained. These were subsequently weaned slowly, depending on the child's need for ongoing pain and anxiety medication, per our unit protocol to minimize the incidence of withdrawal symptoms. Data are shown in the text as mean +/- standard deviation. These 11 children (eight boys and three girls) had an average age of 6.6 +/- 5.6 years (range, 1.2-13 years), average weight of 36.9 +/- 28.7 kg (range, 9.3-95 kg), and burn size of 43 +/- 21.4% (range, 10-85%). Three children had sustained scald burns and eight had flame injuries with associated inhalation injury. They had been intubated for an average of 12.7 +/- 10.9 (range, 2-33 days). Morphine infusions immediately before the initiation of propofol averaged 0.26 +/- 0.31 mg/kg/hour (range, 0.04-1.29 mg/kg/hr) and midazolam averaged 0.15 +/- 0.16 mg/kg/hr (range, 0.06-0.65 mg/kg/hr). Morphine infusions after beginning propofol and at extubation averaged 0.16 +/- 0.16 (range, 0.04-0.65 mg/kg/hr) and midazolam averaged 0.09 +/- 0.08 mg/kg/hr (range, 0.02-0.32 mg/kg/hr). Propofol doses after initial titration during the first hour of infusion averaged 3.6 +/- 2.9 mg/kg/hr (range, 0.4-8.1 mg/kg/hr). Nine of the 11 children (82%) were successfully extubated on the first attempt. Two required reintubation for postextubation stridor 2 to 6 hours after extubation but were successfully extubated the next day after a short course of steroids, again using the same propofol technique. All were awake at extubation and went on to survive. Morphine and midazolam infusions were gradually weaned, and there were no withdrawal symptoms noted. Although prolonged (days) infusions of propofol have been associated with adverse cardiovascular complications in critically ill young children and should probably be avoided, short-term (in hours) use of the drug can facilitate smooth extubation.

Adolescent↗
PubMedDate not supplied

Causes and treatment of burns from grease.

A large number of burns are sustained every year as the result of kitchen grease. A review of a 13-month period at the Joseph M. Still Burn Center in Augusta, Georgia, revealed 60 cases (9.4% of acute burn admissions). Forty-five (75%) of these patients were adults and 25% were children. There were 23 females and 37 males. Forty-two percent of the adults and 33% of the children had some percentage of third-degree injury. The average total body surface area burn in adults was 5.9% and in children 6.3%. There were no deaths in this series. Burns usually occurred as the result of scalds with grease while cooking. Spilling grease on children in the kitchen was a frequent problem. Burns due to ignition of grease was also a cause of injury. Most of the injuries were potentially preventable, and therefore the importance of burn appropriate safety programs is stressed.

Accidents, Home↗
PubMedDate not supplied

Milk bottle burns.

In recent years numerous infants have been treated at Stoke Mandeville Hospital's Burns' Unit for scalds sustained in accidents that occurred during the preparation of warm milk. These were significant burns affecting young children with susceptibly thin skin that often resulted in the injured child requiring a long stay in hospital. Frequently, formal intravenous fluid resuscitation was required as was burn excision and skin grafting. We recommend the use of milk bottle warmer to avoid all the hazards associated with use of different techniques of warming milk bottle.

Accidents, Home↗