Postburn Day Research Articles

Adrenal hemorrhage in a pediatric burn patient

Adrenal hemorrhage with subsequent insufficiency is a rare complication in the burn patient. The case of a previously healthy 3-year-old Latin American male who was a victim of child abuse is presented. He suffered a submersion injury in hot water leading to a 45% total body surface area burn. An acute deterioration on the 7th post burn day was unresponsive to standard inotropic support and cardiopulmonary resuscitation. Post mortem examination revealed bilateral adrenal hemorrhage that had not been present 2 days earlier. To the authors’ knowledge, this is the first reported case in a pediatric burn patient. The clinical manifestations of adrenal insufficiency vary widely and can be easily confused with sepsis. High index of suspicion is necessary for early diagnosis and treatment. Serum cortisol level should be checked and steroid therapy implemented if sepsis syndrome is unresponsive to standard therapy in this setting. This early intervention may be the key to improved survival of the burn patient with a sudden unexplained deterioration resistant to well established resuscitation methods.

Elevation of plasma free PAI-1 levels as an integrated endothelial response to severe burns

To clarify the role of plasminogen activator inhibitor type 1 (PAI-1) in postburn hypercoagulation, we assayed the plasma levels of tissue-type plasminogen activator (t-PA) antigen, total PAI-1 antigen, and total t-PA-PAI-1 complex in 15 burned patients. The total body surface area of the burn injury ranged from 30 to 80%. Serial blood samples were collected from 12 to 168 h following the thermal injury. The plasma t-PA level and the free PAI-1 level increased significantly in the immediate postburn period, and the percent increase in the latter over the values in the healthy controls was much greater than that of the former. The ratio of the concentrations of t-PA-PAI-1 complex to free PAI-1 decreased throughout the 7 postburn days. The fact that the decreases in this ratio clearly showed no dissociation of the euglobulin fraction suggests that the postburn hypofibrinolysis occurred as a result of increased synthesis of PAI-1. On the other hand, changes in several parameters of the coagulation or fibrinolysis system and in plasma thrombomodulin showed that postburn hypercoagulability is associated with secondary hyperfibrinolysis with no evidence of vascular endothelial injury. The praradoxical coexistence of postburn hyper- and hypofibrinolysis is a good reflection of the character of PAI-1, which is a biphasic protein that is both a functional protein and an acute phase reactant. Thus, increased synthesis of PAI-1 may not enhance postburn hypercoagulability to create a coagulation-dominant type of disseminated intravascular coagulation severe enough to trigger multiple organ dysfunction syndrome. In conclusion, increased synthesis of PAI-1 in the initial postburn period reflects an integrated endothelial response to burn stress, and because it is a functional protein, the concentration of free PAI-1 antigen may be an important index for predicting secondary consumption coagulopathy.

Corneal perforation with extrusion of lens in a burn patient

The incidence of ophthalmologic injuries has been reported to be between 20 and 25% in all the burn patients. As most of the eye injuries are associated with severe burns, attention is often directed towards the life-threatening events and eye injuries may be overlooked and undertreated. This case report presents a patient who had 40% flame burn and had recently been transferred from another hospital. He was examined by an ophthalmologist at the referring hospital and it was documented that both of his eyes were normal. He was transferred into the Burns Unit at the Prince of Wales Hospital 8 h later. Unfortunately, all the attention was directed to save his life and it was not until post-burn day 11 that he was found to have right corneal ulceration. Despite vigorous ophthalmologic treatment, the cornea perforated 2 days later with subsequent extrusion of the lens. In view of his grave prognosis with multi-organ failure, he was treated conservatively and he died the following day. It is mandatory to refer patients with facial burns to the ophthalmologist for ocular examination. We recommend that serial eye examinations should be carried out in burn patients who are unconscious or intubated for ventilatory support even if the initial ophthalmologic examinations are normal as the potential risk of serious ocular injuries are high in this particular group of patients.

A primary burn wound does not slow the contraction rate of an adjacent excisional wound.

The response to major burn injury includes systemic release of mediators that may have an effect on wound healing. The authors evaluated the effect of a burn injury on the contraction of an excisional wound adjacent to the burn, and the effect of plasma derived from burn-injured animals on the contraction of the fibroblast-populated collagen matrix (FPCM). Nine rats (90-100 days old) under anesthesia received a standardized 40% total body surface area burn to the dorsum, and eight rats (controls) were sham burned. Immediately thereafter all animals had a square (2.25 cm2) of unburned dermis excised from the dorsum, superior to the burn wound. The excisional wound area was measured at 2 to 3-day intervals postoperatively. Plasma was collected from some animals on postburn day 15; the contraction-stimulating ability of burn vs. control plasma was measured in the FPCM. All animals remained free of sepsis. The excisional wound area in all animals decreased to 50% and then 25% of the initial area after approximately 4 and 8 days respectively. The rate of wound contraction (i.e., wound area reduction) did not differ between burn and control animals. Contraction stimulated by 5% plasma in the FPCM (expressed as a percentage of the original matrix area) was 70.2+/-6.4 (standard deviation) mm2 vs. 62.4 +/-3.9 mm2 for burn vs. control rats respectively (p>0.05). Burn injury in this model did not alter the contraction of an excisional wound at an unburned site. There was no significant difference in the contraction-stimulating ability (FPCM model) of plasma from the burned rats compared with plasma from unburned control rats. Burn injury appears to have an inconsequential effect on the contraction of an adjacent wound.

Thioredoxin blood level increases after severe burn injury.

We have investigated the thioredoxin (TRX) levels in severely burned patients and the possible origin of TRX, based on the recent understanding that TRX is a potent antioxidant with cytoprotective functions. Serum and plasma samples from burns patients and healthy blood donors were collected during the first 10 post-burn days and analyzed in a sandwich TRX enzyme-linked immunosorbent assay (ELISA). The TRX levels found were correlated to a panel of blood tests. The presence of TRX in platelets was investigated by immunoelectron microscopy and Western blotting. TRX serum levels of the severely burned patients showed a significant increase, with a mean serum TRX concentration on the day of injury of 76.5 +/- 19.5 ng/ml (mean +/- SD) and on post-burn day one 122.6 +/- 66.9 ng/ml, compared to control blood donor levels of 22.7 +/- 12.2 ng/ml (p = 0.0041 and 0.0117, respectively). A second peak of increase was found on post-burn days 7 to 9 with a four- to five-fold rise in concentration compared to controls. TRX elevation correlated well with increased platelet (p = 0.007) and leukocyte counts (p = 0.002). We also demonstrated by immunoelectron microscopy and Western blotting the presence of TRX in platelets. In conclusion, our demonstration of TRX release in burn injuries indicates that the TRX system is involved in a rapid antioxidant defense, coagulation processes, cell growth, and control of the extracellular peroxide tone intimately linked to cytoprotection and wound healing in burns. One of the cell types that delivers TRX promptly and efficiently into the blood may be the platelet.

Successful treatment of a case of electrical burn with visceral injury and full-thickness loss of the abdominal wall

A 13-year-old male received high-voltage electrical burns with a resultant large direct wound on the upper abdomen involving the full-thickness of the abdominal wall, including the peritoneum. Early debridement, exploratory laparotomy and temporary restoration of the excised abdominal wall with a fascial prosthesis were carried out at 6 h post-burn. The bilateral upper and right lower limbs were amputated on the 10th post-burn day. The patient developed a 4×4 cm duodenocutaneous fistula on the 28th post-burn day, but was free of peritonitis. After 5 months of the conservative treatment, the fistula closed, and the abdominal wall defect was reconstructed with a free latissimus dorsi musculocutaneous flap. One month later, the patient was discharged following an uneventful recovery.

Anhydrous ammonia burns case report and review of the literature

Chemical burns are associated with significant morbidity, especially anhydrous ammonia burns. Anhydrous ammonia is a colorless, pungent gas that is stored and transported under pressure in liquid form. A 28 year-old patient suffered 45% total body surface area of second and third degree burns as well as inhalational injury from an anhydrous ammonia explosion. Along with fluid resuscitation, the patient’s body was scrubbed every 6 h with sterile water for the first 48 h to decrease the skin pH from 10 to 6–8. He subsequently underwent a total of seven wound debridements; initially with allograft and then autograft. On post burn day 45, he was discharged. The injuries associated with anhydrous ammonia burns are specific to the effects of ammonium hydroxide. Severity of symptoms and tissue damage produced is directly related to the concentration of hydroxyl ions. Liquefactive necrosis results in superficial to full-thickness tissue loss. The affinity of anhydrous ammonia and its byproducts for mucous membranes can result in hemoptysis, pharyngitis, pulmonary edema, and bronchiectasis. Ocular sequelae include iritis, glaucoma, cataracts, and retinal atrophy. The desirability of treating anhydrous ammonia burns immediately cannot be overemphasized. Clothing must be removed quickly, and irrigation with water initiated at the scene and continued for the first 24 h. Resuscitative measures should be started as well as early debridement of nonviable skin. Patients with significant facial or pharyngeal burns should be intubated, and the eyes irrigated until a conjunctivae sac pH below 8.5 is achieved. Although health care professionals need to be prepared to treat chemical burns, educating the public, especially those workers in the agricultural and industrial setting, should be the first line of prevention.

Hepatocyte growth factor modulates the hepatic acute-phase response in thermally injured rats.

Hepatocyte growth factor (HGF) has been shown to modulate the acute-phase response in vitro. The specific in vivo role of HGF in this multifactorial response, however, remains unknown. This study examines the effects of exogenous HGF on the acute-phase response in thermally injured rats. Prospective, randomized, laboratory study. Shriners Hospital for Children and University of Texas Medical Branch laboratories. Fifty-six male Sprague-Dawley rats (weight range, 300-325 g). Animals received a 60% total body surface area third-degree scald burn and were randomly divided to receive either 400 microg/kg/day i.v. HGF or saline (control). Serum acute-phase proteins, cytokines, and insulin-like growth factor (IGF)-I concentrations, as well as liver weight, protein and triglyceride content, IGF-I concentrations, and cytokine gene expression were measured 1, 2, 5, or 7 days after burn. Serum albumin was increased on days 2, 5, and 7 after burn, and transferrin was increased on day 7 after burn in HGF-treated rats compared with controls (p<.05). HGF increased alpha2-macroglobulin concentrations on postburn days 2, 5, and 7 compared with controls (p<.05). Serum interleukin-6 and tumor necrosis factor-alpha were significantly higher within 2 days of burn in rats treated with HGF (p<.05). HGF increased the hepatic gene expression of tumor necrosis factor-alpha compared with controls (p<.05). Serum IGF-I decreased in rats receiving HGF 1, 2, and 5 days after burn, whereas liver IGF-I concentrations were higher on days 1 and 7 after burn compared with controls (p<.05). Hepatic protein concentrations were higher in the HGF group compared with controls on postburn days 1, 2, and 7, with a concomitant increase in total liver weight (p<.05). HGF exerted a strong mitogenic effect on hepatocytes 1 and 2 days after thermal injury compared with controls (p<.05). These findings suggest that HGF modulates the acute-phase response in vivo after burn and causes changes in liver morphology.

The prognostic factors regarding long-term functional outcome of full-thickness hand burns

The treatment of the burned hand has always been a subject of special interest. In order to obtain a better understanding of the parameters involved in the long-term functional outcome of hand burns a retrospective study was performed on 88 consecutive patients with hand burns (143 hands), treated according to a standardised protocol. Patients were followed for at least 12 months postburn. Hand function was assessed by the seven objective test criteria (7-OTC) described by Jebsen. Logistic regression analysis produced five parameters that were found to have a significant predictive value for long-term hand function. In order of predictive value, these were finger amputations, age on admission, impaired autograft take, the full-thickness hand burn surface area and the full-thickness total body burn surface area. By fitting these five variables into an equation, a probability model was obtained, which could be applied to estimate a prognosis concerning the final hand function of an individual patient with a hand burn. No relationship was found between the postburn day of operation and the long-term hand function. This finding is inconsistent with the current consensus that functional outcome is improved by early excision and grafting. In practice, it suggests that hand function is well preserved when burns of uncertain depth are treated expectantly, followed by selective debridement and grafting. Advantages include reduced blood loss, no loss of vital tissue and a reduction of the need for donor sites.

Skin flap survival after superficial and deep partial-thickness burn injury.

Whether a flap can be raised successfully in a body region that has been subjected to burn injury remains an issue. The aim of this study was to investigate the survival of skin flaps that were elevated after superficial and deep partial-thickness burn injury in a rat model. Sixty-five rats were divided into five groups: Group 1 (N = 15) was the control group, group 2 (N = 10) included rats with superficial partial-thickness burns that had flaps elevated on day 0, group 3 (N = 15) was comprised up of rats with superficial partial-thickness burns that had flaps elevated on day 4, group 4 (N = 10) included rats with deep partial-thickness burns that had flaps elevated on day 0, and group 5 (N = 15) was comprised of rats with deep partial-thickness burns that had flaps elevated on day 4. Caudally based dorsal flaps consisting of skin and panniculus carnosus were elevated in all groups, and the amount of surviving tissue on each flap was quantified. The surviving areas of flaps elevated on postburn days 0 and 4 in superficial partial-thickness burn zones (groups 2 and 3) were larger than those of flaps that were elevated on postburn days 0 and 4 in deep partial-thickness burn zones (groups 4 and 5). The surviving portions of flaps that were elevated on day 4 in superficial partial-thickness burn zones (group 3) were similar to the surviving areas of flaps in the control group (group 1), and were larger than those of all other groups (groups 2, 4, and 5). In this rat model, flaps were elevated in superficial dermal burn zones with successful outcomes. However, raising flaps in deep dermal burn zones was not a reliable method.

The 1999 Moyer award. Burn injury induces skeletal muscle apoptosis and the activation of caspase pathways in rats.

Burn injury induces many metabolic disorders, including altered protein kinetics with muscle weakness. The skeletal muscle weakness that occurs as a result of the loss of muscle mass causes hypoventilation and dependence on respirators, a condition that increases morbidity and mortality. The presence or absence of apoptosis in muscle, which can be a cause of the loss of muscle mass, was studied in rats after they had received scald burns to 40% of their body surface areas. The potential pro-apoptotic pathways that were activated were also examined. The burn injury produced did not directly destroy the muscle beneath; muscles just beneath the burned surface showed dramatic apoptotic changes according to assessments with the cell death enzyme-linked immunosorbent assay and in situ TdT-mediated dUTP-X nick-end labeling staining. The extent of apoptosis reached a peak on postburn days 3 and 7. Of note is that apoptosis was also confirmed in muscles at sites distant from the burn injury (eg, tibialis anterior) on both postburn days 3 and 7, a condition that is suggestive of the systemic effects of pro-apoptotic factors. To show that heat itself causes the initiation of the pro-apoptotic signaling, muscle-derived C2C12 cells were subjected to heat treatment at 55 degrees C. Ceramide, a key apoptotic second messenger, was observed to increase in the caveolae fraction but not in non-caveolae fraction of these muscle cells. In muscle tissue from burned rats, stress-activated protein kinase (a downstream-signaling kinase of ceramide) was activated soon after burn injury; this finding is consistent with the hypothesis that ceramide plays a role in burn-induced apoptosis. Caspase-1, -3, and -9, important final apoptotic enzymes involved with the downstream signaling of stress-activated protein kinase, were also activated after burn injury in muscle tissue from burned rats. These findings confirm the hypothesis that apoptosis occurs in skeletal muscle and that major apoptotic pathways are activated after a burn injury. Further characterization of these apoptotic signaling cascades may provide new therapeutic targets for the prevention of burn-induced muscle wasting.

Pseudomonas aeruginosa septicaemia in burns

Out of 1415 patients treated as inpatients at Al-Babtain Center for Burns and Plastic Surgery, Ibn Sina Hospital, Kuwait spanning over a period of 6 years from June 1992 to June 1998, 102 developed clinically and microbiologically proven septicaemia. Only 15 out of them had either single or multiple episodes of septicaemia due to Pseudomonas aeruginosa and were studied during their stay in the hospital. Five of them were males and 10 females, with a mean age of 26 years (range 3–51 years) and mean total body surface area of burns (TBSA) of 66% (range 25–90%). All of them had flame burns and resuscitation was found to be difficult in eight patients either due to delayed hospitalization or accompanied inhalation injury. Seven patients were intubated, four due to inhalation injury and three for septicaemic complications. Among the 15 patients under study, a total of 36 septicaemic episodes were detected of which 21 were due to P. aeruginosa. This organism was found in the first episodes in nine patients, in second episodes in six, in third episodes in three and fourth, fifth and sixth episodes in one patient, each at a variable postburn day. Ten patients had 38 sessions of excision and skin grafting, six of them survived. Nine of the 15 patients under study died due to septicaemia, but only six of them had P. aeruginosa as the last isolate. Except for one, all patients had >40% TBSA burn, two had difficult resuscitation and four were intubated. The day of death varied between 3 to 52 days postburn (mean 19 days). This study showed that females with flame burns are susceptible to P. aeruginosa septicaemia. Difficult resuscitation and intubation also proved to be important risk factors. Septicaemia could occur quite early in the postburn days and the mortality due to this organism was quite high. Early excision and grafting with other effective management may result in a better outcome.

Procalcitonin as a marker for the early diagnosis of severe infection after thermal injury.

High serum concentrations of procalcitonin (PCT), the 116 amino acid precursor protein of the hormone calcitonin, have been found in patients with various bacterial infections, particularly in those with sepsis. Because recent reports have shown that serum PCT constitutes a useful parameter for the diagnosis of sepsis in patients with several clinical conditions, a temporal analysis of the PCT concentrations in the plasma of 19 patients with severe burns (median body surface area burned, 32%) was conducted retrospectively. Nine patients were classified as septic on the basis of standardized clinical and laboratory parameters. Compared with the nonseptic group, these patients showed higher plasma PCT throughout the study period (median concentrations of septic vs nonseptic patient groups: 0.4 vs. 0.2 microg/L on postburn day 2; 1.0 vs. 0.3 microg/L on postburn day 4; 5.5 vs. 0.3 microg/L on postburn day 7; 10.8 vs. 0.5 microg/L on postburn day 9; 4.2 vs. 0.4 microg/L on postburn day 12; and 1.7 vs. 0.5 microg/L on postburn day 14), with differences considered to be significant (P<.05) from day 7 on. In contrast, differences in the plasma C-reactive protein concentrations were less pronounced and never reached statistical significance. PCT concentrations exceeding 15 microg/L were only observed in the 3 patients who died of sepsis-induced multiple organ failure. In addition to absolute PCT, individual time courses were also of diagnostic value. PCT is a highly efficient laboratory parameter for the diagnosis of severe infectious complications after a burn injury.

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.

A unique mechanism of desensitization to lipolysis mediated by beta(3)-adrenoceptor in rats with thermal injury.

Thermal injury causes a hypermetabolic state associated with increased levels of catabolic hormones, but the molecular bases for the metabolic abnormalities are poorly understood. We investigated the lipolytic responses after beta(3)-adrenoceptor (beta(3)-AR) agonists and evaluated the associated changes in beta-AR and its downstream signaling molecules in adipocytes isolated from rats with thermal injury. Maximal lipolytic responses to a specific beta(3)-AR agonist, BRL-37344, were significantly attenuated at post burn days (PBD) 3 and 7. Despite significant reduction of the cell surface beta(3)-AR number and its mRNA at PBD 3 and 7, BRL-37344 and forskolin-stimulated cAMP levels were not decreased. Glycerol production in response to dibutyryl cAMP, a direct stimulant of hormone-sensitive lipase (HSL) via protein kinase A (PKA), was significantly attenuated. Although immunoblot analysis indicated no differences in the expression and activity of PKA or in the expression of HSL, HSL activity showed significant reductions. Finally, beta(3)-AR-induced insulin secretion was indeed attenuated in vivo. These studies indicate that the beta(3)-AR system is desensitized after burns, both in the adipocytes and in beta(3)-AR-induced secretion of insulin. Furthermore, these data suggest a complex and unique mechanism underlying the altered signaling of lipolysis at the level of HSL in animals after burns.

Increased Expression of Insulin-like Growth Factor-I in Serum and Liver after Recombinant Human Growth Hormone Administration in Thermally Injured Rats

Background. Recombinant human growth hormone (rhGH) has been shown to modulate the hypermetabolic response and the hepatic acute-phase response after thermal injury. In vitro studies, however, demonstrated that rhGH activates insulin-like growth factor-I (IGF-I) gene transcription and production, suggesting that rhGH may exert some of its effects indirectly through IGF-I stimulation. The purpose of this study was to determine the effects of rhGH on serum and hepatic IGF-I in thermally injured rats.Methods. Sprague–Dawley rats (56 males) receiving a 60% TBSA third-degree scald burn were randomly divided to receive either rhGH (2.5 mg/kg/day im) or saline (control). Rats were sacrificed on postburn days 1, 2, 5, and 7 and serum IGF-I, hepatic IGF-I mRNA, and IGF-I protein concentration were measured. The physiologic response to changes in IGF-I levels was evaluated by measuring hepatocyte proliferation, total liver protein concentration, and muscle dry/wet weights.Results. Serum IGF-I was increased from postburn day 1 through day 7 in rats receiving rhGH compared to controls (P < 0.05). Hepatic IGF-I mRNA and IGF-I protein expression were increased from day 1 to 7 after burn in animals receiving rhGH when compared to controls (P < 0.05). Recombinant hGH increased hepatocyte proliferation at 5 days and total liver protein concentration at 5 and 7 days postburn compared to controls (P < 0.05). Muscle dry/wet weights increased in rats receiving rhGH at 7 days after burn compared to controls (P < 0.05).Summary. Liver and serum IGF-I levels decreased after a thermal injury. Recombinant hGH attenuated this decrease by stimulating hepatic IGF-I expression. Increases in IGF-I were associated with increases in hepatocyte proliferation and protein concentration in liver and muscle.Conclusion. We suggest that rhGH modulates the hypermetabolic response through IGF-I stimulation in the hepatic parenchyma.

Recombinant Human Growth Hormone Alters Acute Phase Reactant Proteins, Cytokine Expression, and Liver Morphology in Burned Rats

Background.The effects of exogenous recombinant human growth hormone (rhGH) on hepatic acute phase reactant proteins, cytokine expression, and liver morphology were studied in thermally injured rats to define whether rhGH alters the acute phase response.Materials and methods.Sprague-Dawley rats (56 males) receiving a 60% TBSA third-degree scald burn were randomly divided into two groups to receive either 2.5 mg/kg/day sc rhGH or saline. Rats were sacrificed on Postburn Days 1, 2, 5, and 7. Serum acute phase reactant proteins and cytokines TNF-α, IL-1α, IL-1β, and IL-6 were measured. Hepatocyte proliferation, hepatic cytokine gene expression, and liver protein concentrations were determined.Results.Recombinant hGH increased serum albumin on Days 5 and 7 after burn (P< 0.05). Serum haptoglobin and α1-acid glycoprotein levels decreased at 2, 5, and 7 days after burn compared to saline (P< 0.05). In rats treated with rhGH, serum IL-1β decreased 1 day postburn, while serum TNF-α increased 5 days after burn compared to saline (P< 0.05). Serum IL-6 and IL-1α did not change. Hepatic RNA levels for TNF-α were significantly elevated on Day 1 postburn compared to saline (P< 0.05). Hepatic protein content increased on Days 2, 5, and 7 postburn compared to saline (P< 0.05). Hepatocyte proliferation in rhGH-treated rats increased on Day 5 after burn (P< 0.05).Conclusion.Data indicate that rhGH alters the hepatic acute phase response by decreasing type I acute phase proteins and modulating IL-1-like cytokine expression. These changes are associated with increased hepatocyte mitosis and serum and total liver protein concentrations.

Beta-haemolytic Streptococcus infection in burns

Group A beta haemolytic Streptococcus has been one of the most serious infections in the burn patients resulting in severe cellulitis and sepsis. Penicillin has been used ever since its introduction as prophylaxis against these conditions. Penicillin prophylaxis was used in our burn unit as well without any serious evaluation until December 1992. This prospective study was therefore, undertaken to evaluate the incidence of beta haemolytic Streptococcus infection in burn patients, and its clinical outcome over a period of 5 years in the absence of prophylaxis with penicillin. 14 of the 1213 burn patients admitted to the Al-Babtain Centre for Plastic Surgery and Burns from January 1993 to December 1997 had either colonization or infection with Streptococcus spp. Their mean age was 15 years (range 1 month to 52 years) and the mean burn surface area was 20% (range 5 to 90%). Streptococci were isolated from burn wounds in 10 patients, throat in 3 and blood culture in 1. Group A Streptococcus was found in 5, group C in 3 and group D in 6 patients. In all patients except one the organisms were isolated ≥72 h post burn. The infections were successfully controlled by antibiotic and no detrimental effect was observed either on wound healing or skin graft take. There was no mortality amongst these 14 patients. The study showed that only 1.1% of the burn patients in our unit acquired Streptococcus of which only one third comprised of group A. This study thus demonstrates that the practice of penicillin prophylaxis during the first five post burn days may not be of any value and therefore, deserves discontinuation in units where the incidence of this organism is minuscule.

Expression of midkine in normal and burn sites of rat skin

Expression of midkine (MK), a retinoic acid-inducible heparin binding growth factor, was examined immunohistochemically in normal and burn sites of rat skin. In the normal skin, MK was localized in the epidermis and dermal appendages such as hair follicles and sebaceous glands. Mast cells in the subdermal connective tissue also accumulated MK. After burn injury, MK-positive cells began to infiltrate into subdermal connective tissue, and the number of MK-positive cells in the region increased to a maximum at postburn day two and then decreased gradually. Western blotting analysis of both normal and postburn skin revealed a 30 kDa band reactive with anti-MK antibody; this band was concluded to be a dimer of MK. These findings were discussed from the viewpoint of the possible role of MK in wound healing.

Changes in gut mucosal nitric oxide synthase (NOS) activity after thermal injury and its relation with barrier failure.

This study was designed to investigate changes in mucosal NOS activity after burns and its relation to barrier failure. In Experiment 1, female specific pathogen free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. One to six days after burn, intestinal permeability was determined from the plasma leakage of fluorescein isothiocyanate (FITC)-dextran 4400, intestinal mucosal cNOS and iNOS activity were assayed using Griess' reagent, and the cellular localization of iNOS was examined using immunostaining. In Experiment 2, S-methylisothiourea (SMT) was given (5 mg/kg, i.p. every 12 h) for 2 days to suppress inducible NOS (iNOS) activity after thermal injury. On postburn Day 2, the effect of SMT on gut mucosal NOS activity, intestinal permeability, and barrier function were evaluated. The activity of iNOS increased 24 h after the injury and up to a maximum of twofold on postburn Day 2, and decreased thereafter. The increase in iNOS activity in gut mucosa correlated well with the increase in intestinal permeability, an index for barrier failure (r = .776, p = .0002). Results from iNOS immunostaining showed that changes in mucosal iNOS activity after the burn occurred mainly in the enterocytes rather than in the macrophages. Administration of SMT decreased mucosal iNOS activity, intestinal permeability, and bacterial translocation incidence to mesenteric lymph node concurrently. In conclusion, thermal injury induces intestinal mucosal iNOS, which is principally in the enterocytes. The increased intestinal iNOS activity was closely related to barrier failure. SMT inhibited intestinal mucosal iNOS activity and prevented barrier failure as demonstrated by a decrease in BT occurrence and intestinal permeability.