S. Wolf - Academia.edu (original) (raw)

Papers by S. Wolf

Journal of Trauma and Acute Care Surgery

In 2012, the National Healthcare Safety Network presented a new surveillance definition for venti... more In 2012, the National Healthcare Safety Network presented a new surveillance definition for ventilator-associated events (VAEs) to objectively define worsening pulmonary status in ventilated patients. VAE subcategories, ventilator-associated condition (VAC), infection-related VAC, and probable ventilator-associated pneumonia (PrVAP), were vetted predominantly in medical intensive care units. Our goal was to evaluate how well VAE criteria characterize pulmonary complications in surgical intensive care unit (SICU) patients. Since September 2012, all intubated SICU patients were screened prospectively for VAE and monitored for sustained respiratory dysfunction that did not meet VAE criteria. We diagnosed ventilator-associated pneumonia (VAP) using a clinical definition: Clinical Pulmonary Infection Score (CPIS) greater than 6 and catheter-directed bronchoalveolar lavage cultures with 10 or more colony-forming units per milliliter of pathogenic organisms. We admitted 704 intubated patie...

Shock, 2002

Severe cutaneous bum alters gut epithelial homeostasis. In previous studies, treatment with bombe... more 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.

Journal of Burn Care & Research, 2007

Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediator... more Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediators. Thus, burn patients, by definition, already have "systemic inflammatory response syndrome." Current definitions for sepsis and infection have many criteria (fever, tachycardia, tachypnea, leukocytosis) that are routinely found in patients with extensive burns, making these current definitions less applicable to the burn population. Experts in burn care and research, all members of the American Burn Association, were asked to review the literature and prepare a potential definition on one topic related to sepsis or infection in burn patients. On January 20, 2007, the participants met in Tucson, Arizona to develop consensus for these definitions. After review of the definitions, a summary of the proceedings was prepared. The goal of the consensus conference was to develop and publish standardized definitions for sepsis and infection-related diagnoses in the burn population. Standardized definitions will improve the capability of performing more meaningful multicenter trials among burn centers.

Critical Care Medicine, 2002

The purpose of this study was to assess if hyperglycemia influences energy expenditure or the ext... more The purpose of this study was to assess if hyperglycemia influences energy expenditure or the extent of muscle protein catabolism in severely burned adults. Retrospective study. Burn intensive care unit at a university hospital. Adults with burns on >/=40% of their body surface area. Simultaneous measurement of indirect calorimetry and leg net balance of phenylalanine (as an index of muscle protein catabolism). Patients were stratified by plasma glucose values at the time of metabolic measurements (i.e., normal, glucose at </=130 mg/dL; mild hyperglycemia, glucose at 130-200 mg/dL; severe hyperglycemia, glucose at >200 mg/dL). Normal (n = 9; plasma glucose, 109 +/- 13 mg/dL [mean +/- sd]), mildly hyperglycemic (n = 13l plasma glucose, 156 +/- 17 mg/dL), and severely hyperglycemic subjects (n = 7, glucose 231 +/- 32 mg/dL) were similar in age, body weight, extent of burn area, and daily caloric intake. Severe hyperglycemia was associated with significantly higher arterial concentrations of phenylalanine (normal, 0.079 +/- 0.027 micromol/L; severe hyperglycemia, 0.116 +/- 0.028; p <.05) and a significantly greater net efflux of phenylalanine from the leg (normal, -0.067 +/- 0.072 micromol.min(-1).100 mL(-1) leg volume; severe hyperglycemia, -0.151 +/- 0.080 micromol.min(-1).100 mL(-1) leg volume; p <.05). Resting energy expenditure and respiratory quotient were similar between patient groups. These findings demonstrate an association between hyperglycemia and an increased rate of muscle protein catabolism in severely burned patients. This suggests a possible link between resistance of muscle to the action of insulin for both glucose clearance and muscle protein catabolism.

Surgery, 2000

The hypermetabolic response to severe burn is characterized by muscle protein catabolism. Current... more The hypermetabolic response to severe burn is characterized by muscle protein catabolism. Current opinion states that the hypermetabolic state resolves soon after complete wound closure. Clinically, we have witnessed that burned children appear to be hypermetabolic and catabolic long after full healing of their wounds. Our goal in this study was to determine scientifically if burn-associated hypermetabolism persists after full wound healing. To determine the duration of muscle catabolism and systemic hypermetabolism after severe burn in children, patients with > 40% total body surface area burns were enrolled in a prospective, longitudinal study; resting energy expenditure was measured by indirect calorimetry, muscle protein kinetics were determined by using stable isotopic methodology, and body composition was measured by dual-energy x-ray absorptiometry imaging. Data were collected at 6, 9, and 12 months after injury. The mean total body surface area burned was 65% +/- 13%, and the mean age was 7.6 +/- 1. 5 years. Resting energy expenditure was elevated above the predicted age-matched levels from the Harris-Benedict equation and incrementally declined throughout the 12-month study. The net protein balance and lean mass reflected catabolic persistence at 6 and 9 months after severe burn. Between 9 and 12 months, protein breakdown decreased, net protein balance improved, and lean body mass increased. In severely burned children, hypermetabolism and catabolism remain exaggerated for at least 9 months after injury. This suggests that therapeutic attempts to manipulate the catabolic and hypermetabolic response to severe injury should be continued long after injury.

Shock, 2003

Severe burn induces the hepatic acute phase response. We previously showed that recombinant human... more Severe burn induces the hepatic acute phase response. We previously showed that recombinant human growth hormone (GH) treatment after burn down-regulated acute phase protein (APP) production and gene expression in vivo. In this study, we hypothesized that the inhibitory effect of GH on the hepatic acute phase response was due to increased suppressor of cytokine signaling (SOCS) gene expression. HepG2 cells were treated with Interleukin-1beta (IL-1beta; 2 ng/mL) and interleukin 6 (IL-6; 20 ng/mL) alone or combined with GH (2 microg/mL) for 15 and 30 min, and 1, 2, and 4 h. The levels of gene expression for alpha1-acid glycoprotein (AGP), alpha1-antitrypsin (ATT), and SOCS (CIS, SOCS-1, 2, and 3) were measured by reverse transcript-polymerase chain reaction (RT-PCR). APP levels in the supernatant were determined by enzyme-linked immunosorbent sandwich assay (ELISA). The gene expression of AGP and ATT were also measured in HepG2 cells transfected with pEF-Flag-l/mSOCS-3 plasmid after IL-1beta or IL-6 treatment. Data are expressed as means +/- SEM, and statistical analysis was performed by one- or two-way analysis of variance. IL-1beta and IL-6 induced AGP and ATT gene expression and protein production, respectively, which was down-regulated by GH treatment. SOCS-3 but not CIS, SOCS-1, or SOCS-2 gene expression was significantly increased by GH treatment. APP gene expression was significantly decreased in cells transfected with plasmid over expressing SOCS-3 after IL-6 and IL-1beta treatment. GH attenuates IL-1beta or IL-6 induced APP gene expression, which is associated with increased expression of SOCS-3. This study suggests that SOCS-3 plays an important role in the suppression of cytokine signaling by GH in down-regulating the acute phase response after injury.

The Surgical clinics of North America, 2014

This review demonstrates that many advances have been made in burn care that have made dramatic d... more This review demonstrates that many advances have been made in burn care that have made dramatic differences in mortality, clinical outcomes, and quality of life in burn survivors; however, much work remains. In reality, the current standard of care is insufficient and we cannot be satisfied with the status quo. We must strive for the following goals: no deaths due to burn, no scarring, and no pain. These particular goals have only begun to be confronted.

Secondary infections after burn are common and are a major contributor to morbidity and mortality... more Secondary infections after burn are common and are a major contributor to morbidity and mortality. We previously showed that burn disrupted proximal gut mucosal homeostasis through increased epithelial cell apoptosis. In the present study, we sought to determine whether proximal gut mucosal disruption is additively affected by secondary endotoxemia after a severe burn. C57BL/6 mice received 30% total body surface area full-thickness scald burns and were randomized to receive saline or LPS 1 mg/kg body weight given intraperitoneally 72 h after burn. Proximal small bowel was harvested 12 h after LPS injection. Mucosal height and epithelial cell number were assessed on hematoxylin-eosin sections, intestinal epithelial cell apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen. Results showed that proximal gut mucosa impairment occurred 12 h after injury, including significantly decreased proximal gut wet weight, gut mucosal height, and epithelial cell number associated with increased proximal gut epithelial apoptosis (P < 0.05). This impairment diminished 72 h after burn. Second-hit endotoxemia caused additional proximal gut mucosa damage with decreased proximal gut weight, cell number, and mucosal height (P < 0.05) and significantly increased small intestinal epithelial apoptosis and mucosal atrophy, even after the first event, indicating a second detrimental effect of endotoxemia after the initial injury.

Surgery, 2004

Severe burn induces the hepatic acute phase response. In this study, we wondered whether continuo... more Severe burn induces the hepatic acute phase response. In this study, we wondered whether continuous insulin treatment decreases acute phase protein levels in the severely burned. Eighteen children aged 2 to 17 years with burns >40% of total body surface area were randomized to receive either insulin (n=9) or no treatment (n=9) within 72 hours after injury until the wounds were 95% healed. Insulin was given at a continuous rate of > or =1.5 microU/kg/min to maintain euglycemia (serum glucose 100-140 microg/dL). Plasma was examined at days 7, 14, 21, and 28 for acute phase protein levels including C-reactive protein, C3 complement, alpha1-acid glycoprotein, haptoglobin, alpha2-macroglobulin, prealbumin, transferrin, and retinol-binding protein. Statistical analysis was by ANOVA and t test. With insulin treatment, alpha1-acid glycoprotein, C3 complement, alpha2-macroglobulin, and haptoglobin levels decreased (P<.05) after a severe burn compared with control, especially at days 21 and 28. Additionally, the hepatic constitutive proteins (prealbumin, transferrin, and retinol-binding protein) were lower in the insulin-treatment group than those of the control group at day 21 (P<.05). Continuous insulin treatment decreases acute phase protein levels after a severe burn. The results suggest insulin downregulation of the hepatic acute phase response to injury.

Pediatric Surgery International, 1997

Active basic-science investigations and directed clinical research have resulted in effective the... more Active basic-science investigations and directed clinical research have resulted in effective therapies for improving the outcomes of burned children. Major areas of inquiry have been in resuscitation, hypermetabolism, wound coverage, and inhalation injury, all of which have yielded fruitful results. Probably the most important advance has been the widespread use of early excision and grafting, which has changed the pathophysiology of burn injury. Further advances in the fields of metabolism, wound healing, and respiratory medicine may improve results even further, particularily in functional and cosmetic outcomes.

New England Journal of Medicine, 2001

The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expend... more The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expenditure and muscle-protein catabolism. We hypothesized that blockade of b -adrenergic stimulation with propranolol would decrease resting energy expenditure and muscle catabolism in patients with severe burns.

Journal of The American College of Surgeons, 2000

Background: Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mu... more Background: Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mucosal integrity. We recently showed that burn also increases gut epithelial cell death by apoptosis. The goal of this study was to determine whether changes in gut perfusion after burn contribute to burn-associated gut apoptosis.Study Design: We first correlated superior mesenteric artery blood flow with measurement of gut perfusion

Journal of Surgical Research, 2011

Background-Previous studies have shown that starvation induces small bowel atrophy, and that atro... more Background-Previous studies have shown that starvation induces small bowel atrophy, and that atrophy diminishes with aging. In this experiment, we assessed whether starvation-induced atrophy of proximal gut mucosa is associated with the Interleukin-1 receptor (IL-1R) signaling pathway in aged mice.

Gastroenterology, 2001

To investigate the effect of LPS on human hepatocytes and study whether recombinant human growth ... more To investigate the effect of LPS on human hepatocytes and study whether recombinant human growth hormone (rhGH) could protect hepatocytes from apoptosis induced by LPS. HepG(2) cells were treated with LPS (20 microg/ml) or LPS and rhGH for 16 hours. The apoptosis of HepG(2) cells was detected by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) or electron microscopy. HepG(2) cells treated with LPS exhibited some specific morphological features of typical apoptosis. the percentage of apoptotic cells in HepG(2) cells treated with LPS and hrGH was significantly lower than that treated with LPS (36+/-5.6)% vs (99+/-0.8)%, P<0.001). LPS can induce apoptosis of HepG(2) cells, and hrGH can downregulate the apoptotic role of LPS on HepG(2) cells.

Archives of Surgery, 2002

Advances in burn treatment including early excision of the wound have increased survival in patie... more Advances in burn treatment including early excision of the wound have increased survival in patients treated at specialized burn centers. We hypothesized that the patients with delayed wound excision and grafting would experience deleterious outcomes. From 1995 to 1999, 157 children with acute burns covering 40% or more of total body surface area and having more than 10% of full-thickness burns were admitted to our institution within 2 weeks of injury. Among them, 86, 42, and 29 patients underwent first operation on days 0 to 2, days 3 to 6, and days 7 to 14 after burn, respectively. Outcomes observed were mortality, number of operative procedures, length of hospitalization, blood transfused, incidence of wound bacterial and fungal contamination, invasive wound infection, and sepsis. Demographic data for the groups showed no differences in sex or total body surface area burned. Mortality and number of operative procedures and blood transfusions were not different between groups. Hospitalizations were longer in the delayed groups, which was associated with a higher incidence of significant wound contamination (P =.008). Invasive wound infection also increased significantly with delay of excision (P<.001). An increased incidence of sepsis was seen in patients with delayed wound excision and grafting (P =.04). Delays in excision were associated with longer hospitalization and delayed wound closure, as well as increased rates of invasive wound infection and sepsis. Our data indicate that early excision within 48 hours is optimal for pediatric patients with massive burns.

Journal of Trauma and Acute Care Surgery

In 2012, the National Healthcare Safety Network presented a new surveillance definition for venti... more In 2012, the National Healthcare Safety Network presented a new surveillance definition for ventilator-associated events (VAEs) to objectively define worsening pulmonary status in ventilated patients. VAE subcategories, ventilator-associated condition (VAC), infection-related VAC, and probable ventilator-associated pneumonia (PrVAP), were vetted predominantly in medical intensive care units. Our goal was to evaluate how well VAE criteria characterize pulmonary complications in surgical intensive care unit (SICU) patients. Since September 2012, all intubated SICU patients were screened prospectively for VAE and monitored for sustained respiratory dysfunction that did not meet VAE criteria. We diagnosed ventilator-associated pneumonia (VAP) using a clinical definition: Clinical Pulmonary Infection Score (CPIS) greater than 6 and catheter-directed bronchoalveolar lavage cultures with 10 or more colony-forming units per milliliter of pathogenic organisms. We admitted 704 intubated patie...

Shock, 2002

Severe cutaneous bum alters gut epithelial homeostasis. In previous studies, treatment with bombe... more 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.

Journal of Burn Care & Research, 2007

Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediator... more Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediators. Thus, burn patients, by definition, already have "systemic inflammatory response syndrome." Current definitions for sepsis and infection have many criteria (fever, tachycardia, tachypnea, leukocytosis) that are routinely found in patients with extensive burns, making these current definitions less applicable to the burn population. Experts in burn care and research, all members of the American Burn Association, were asked to review the literature and prepare a potential definition on one topic related to sepsis or infection in burn patients. On January 20, 2007, the participants met in Tucson, Arizona to develop consensus for these definitions. After review of the definitions, a summary of the proceedings was prepared. The goal of the consensus conference was to develop and publish standardized definitions for sepsis and infection-related diagnoses in the burn population. Standardized definitions will improve the capability of performing more meaningful multicenter trials among burn centers.

Critical Care Medicine, 2002

The purpose of this study was to assess if hyperglycemia influences energy expenditure or the ext... more The purpose of this study was to assess if hyperglycemia influences energy expenditure or the extent of muscle protein catabolism in severely burned adults. Retrospective study. Burn intensive care unit at a university hospital. Adults with burns on >/=40% of their body surface area. Simultaneous measurement of indirect calorimetry and leg net balance of phenylalanine (as an index of muscle protein catabolism). Patients were stratified by plasma glucose values at the time of metabolic measurements (i.e., normal, glucose at </=130 mg/dL; mild hyperglycemia, glucose at 130-200 mg/dL; severe hyperglycemia, glucose at >200 mg/dL). Normal (n = 9; plasma glucose, 109 +/- 13 mg/dL [mean +/- sd]), mildly hyperglycemic (n = 13l plasma glucose, 156 +/- 17 mg/dL), and severely hyperglycemic subjects (n = 7, glucose 231 +/- 32 mg/dL) were similar in age, body weight, extent of burn area, and daily caloric intake. Severe hyperglycemia was associated with significantly higher arterial concentrations of phenylalanine (normal, 0.079 +/- 0.027 micromol/L; severe hyperglycemia, 0.116 +/- 0.028; p <.05) and a significantly greater net efflux of phenylalanine from the leg (normal, -0.067 +/- 0.072 micromol.min(-1).100 mL(-1) leg volume; severe hyperglycemia, -0.151 +/- 0.080 micromol.min(-1).100 mL(-1) leg volume; p <.05). Resting energy expenditure and respiratory quotient were similar between patient groups. These findings demonstrate an association between hyperglycemia and an increased rate of muscle protein catabolism in severely burned patients. This suggests a possible link between resistance of muscle to the action of insulin for both glucose clearance and muscle protein catabolism.

Surgery, 2000

The hypermetabolic response to severe burn is characterized by muscle protein catabolism. Current... more The hypermetabolic response to severe burn is characterized by muscle protein catabolism. Current opinion states that the hypermetabolic state resolves soon after complete wound closure. Clinically, we have witnessed that burned children appear to be hypermetabolic and catabolic long after full healing of their wounds. Our goal in this study was to determine scientifically if burn-associated hypermetabolism persists after full wound healing. To determine the duration of muscle catabolism and systemic hypermetabolism after severe burn in children, patients with > 40% total body surface area burns were enrolled in a prospective, longitudinal study; resting energy expenditure was measured by indirect calorimetry, muscle protein kinetics were determined by using stable isotopic methodology, and body composition was measured by dual-energy x-ray absorptiometry imaging. Data were collected at 6, 9, and 12 months after injury. The mean total body surface area burned was 65% +/- 13%, and the mean age was 7.6 +/- 1. 5 years. Resting energy expenditure was elevated above the predicted age-matched levels from the Harris-Benedict equation and incrementally declined throughout the 12-month study. The net protein balance and lean mass reflected catabolic persistence at 6 and 9 months after severe burn. Between 9 and 12 months, protein breakdown decreased, net protein balance improved, and lean body mass increased. In severely burned children, hypermetabolism and catabolism remain exaggerated for at least 9 months after injury. This suggests that therapeutic attempts to manipulate the catabolic and hypermetabolic response to severe injury should be continued long after injury.

Shock, 2003

Severe burn induces the hepatic acute phase response. We previously showed that recombinant human... more Severe burn induces the hepatic acute phase response. We previously showed that recombinant human growth hormone (GH) treatment after burn down-regulated acute phase protein (APP) production and gene expression in vivo. In this study, we hypothesized that the inhibitory effect of GH on the hepatic acute phase response was due to increased suppressor of cytokine signaling (SOCS) gene expression. HepG2 cells were treated with Interleukin-1beta (IL-1beta; 2 ng/mL) and interleukin 6 (IL-6; 20 ng/mL) alone or combined with GH (2 microg/mL) for 15 and 30 min, and 1, 2, and 4 h. The levels of gene expression for alpha1-acid glycoprotein (AGP), alpha1-antitrypsin (ATT), and SOCS (CIS, SOCS-1, 2, and 3) were measured by reverse transcript-polymerase chain reaction (RT-PCR). APP levels in the supernatant were determined by enzyme-linked immunosorbent sandwich assay (ELISA). The gene expression of AGP and ATT were also measured in HepG2 cells transfected with pEF-Flag-l/mSOCS-3 plasmid after IL-1beta or IL-6 treatment. Data are expressed as means +/- SEM, and statistical analysis was performed by one- or two-way analysis of variance. IL-1beta and IL-6 induced AGP and ATT gene expression and protein production, respectively, which was down-regulated by GH treatment. SOCS-3 but not CIS, SOCS-1, or SOCS-2 gene expression was significantly increased by GH treatment. APP gene expression was significantly decreased in cells transfected with plasmid over expressing SOCS-3 after IL-6 and IL-1beta treatment. GH attenuates IL-1beta or IL-6 induced APP gene expression, which is associated with increased expression of SOCS-3. This study suggests that SOCS-3 plays an important role in the suppression of cytokine signaling by GH in down-regulating the acute phase response after injury.

The Surgical clinics of North America, 2014

This review demonstrates that many advances have been made in burn care that have made dramatic d... more This review demonstrates that many advances have been made in burn care that have made dramatic differences in mortality, clinical outcomes, and quality of life in burn survivors; however, much work remains. In reality, the current standard of care is insufficient and we cannot be satisfied with the status quo. We must strive for the following goals: no deaths due to burn, no scarring, and no pain. These particular goals have only begun to be confronted.

Secondary infections after burn are common and are a major contributor to morbidity and mortality... more Secondary infections after burn are common and are a major contributor to morbidity and mortality. We previously showed that burn disrupted proximal gut mucosal homeostasis through increased epithelial cell apoptosis. In the present study, we sought to determine whether proximal gut mucosal disruption is additively affected by secondary endotoxemia after a severe burn. C57BL/6 mice received 30% total body surface area full-thickness scald burns and were randomized to receive saline or LPS 1 mg/kg body weight given intraperitoneally 72 h after burn. Proximal small bowel was harvested 12 h after LPS injection. Mucosal height and epithelial cell number were assessed on hematoxylin-eosin sections, intestinal epithelial cell apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen. Results showed that proximal gut mucosa impairment occurred 12 h after injury, including significantly decreased proximal gut wet weight, gut mucosal height, and epithelial cell number associated with increased proximal gut epithelial apoptosis (P < 0.05). This impairment diminished 72 h after burn. Second-hit endotoxemia caused additional proximal gut mucosa damage with decreased proximal gut weight, cell number, and mucosal height (P < 0.05) and significantly increased small intestinal epithelial apoptosis and mucosal atrophy, even after the first event, indicating a second detrimental effect of endotoxemia after the initial injury.

Surgery, 2004

Severe burn induces the hepatic acute phase response. In this study, we wondered whether continuo... more Severe burn induces the hepatic acute phase response. In this study, we wondered whether continuous insulin treatment decreases acute phase protein levels in the severely burned. Eighteen children aged 2 to 17 years with burns >40% of total body surface area were randomized to receive either insulin (n=9) or no treatment (n=9) within 72 hours after injury until the wounds were 95% healed. Insulin was given at a continuous rate of > or =1.5 microU/kg/min to maintain euglycemia (serum glucose 100-140 microg/dL). Plasma was examined at days 7, 14, 21, and 28 for acute phase protein levels including C-reactive protein, C3 complement, alpha1-acid glycoprotein, haptoglobin, alpha2-macroglobulin, prealbumin, transferrin, and retinol-binding protein. Statistical analysis was by ANOVA and t test. With insulin treatment, alpha1-acid glycoprotein, C3 complement, alpha2-macroglobulin, and haptoglobin levels decreased (P<.05) after a severe burn compared with control, especially at days 21 and 28. Additionally, the hepatic constitutive proteins (prealbumin, transferrin, and retinol-binding protein) were lower in the insulin-treatment group than those of the control group at day 21 (P<.05). Continuous insulin treatment decreases acute phase protein levels after a severe burn. The results suggest insulin downregulation of the hepatic acute phase response to injury.

Pediatric Surgery International, 1997

Active basic-science investigations and directed clinical research have resulted in effective the... more Active basic-science investigations and directed clinical research have resulted in effective therapies for improving the outcomes of burned children. Major areas of inquiry have been in resuscitation, hypermetabolism, wound coverage, and inhalation injury, all of which have yielded fruitful results. Probably the most important advance has been the widespread use of early excision and grafting, which has changed the pathophysiology of burn injury. Further advances in the fields of metabolism, wound healing, and respiratory medicine may improve results even further, particularily in functional and cosmetic outcomes.

New England Journal of Medicine, 2001

The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expend... more The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expenditure and muscle-protein catabolism. We hypothesized that blockade of b -adrenergic stimulation with propranolol would decrease resting energy expenditure and muscle catabolism in patients with severe burns.

Journal of The American College of Surgeons, 2000

Background: Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mu... more Background: Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mucosal integrity. We recently showed that burn also increases gut epithelial cell death by apoptosis. The goal of this study was to determine whether changes in gut perfusion after burn contribute to burn-associated gut apoptosis.Study Design: We first correlated superior mesenteric artery blood flow with measurement of gut perfusion

Journal of Surgical Research, 2011

Background-Previous studies have shown that starvation induces small bowel atrophy, and that atro... more Background-Previous studies have shown that starvation induces small bowel atrophy, and that atrophy diminishes with aging. In this experiment, we assessed whether starvation-induced atrophy of proximal gut mucosa is associated with the Interleukin-1 receptor (IL-1R) signaling pathway in aged mice.

Gastroenterology, 2001

To investigate the effect of LPS on human hepatocytes and study whether recombinant human growth ... more To investigate the effect of LPS on human hepatocytes and study whether recombinant human growth hormone (rhGH) could protect hepatocytes from apoptosis induced by LPS. HepG(2) cells were treated with LPS (20 microg/ml) or LPS and rhGH for 16 hours. The apoptosis of HepG(2) cells was detected by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) or electron microscopy. HepG(2) cells treated with LPS exhibited some specific morphological features of typical apoptosis. the percentage of apoptotic cells in HepG(2) cells treated with LPS and hrGH was significantly lower than that treated with LPS (36+/-5.6)% vs (99+/-0.8)%, P<0.001). LPS can induce apoptosis of HepG(2) cells, and hrGH can downregulate the apoptotic role of LPS on HepG(2) cells.

Archives of Surgery, 2002

Advances in burn treatment including early excision of the wound have increased survival in patie... more Advances in burn treatment including early excision of the wound have increased survival in patients treated at specialized burn centers. We hypothesized that the patients with delayed wound excision and grafting would experience deleterious outcomes. From 1995 to 1999, 157 children with acute burns covering 40% or more of total body surface area and having more than 10% of full-thickness burns were admitted to our institution within 2 weeks of injury. Among them, 86, 42, and 29 patients underwent first operation on days 0 to 2, days 3 to 6, and days 7 to 14 after burn, respectively. Outcomes observed were mortality, number of operative procedures, length of hospitalization, blood transfused, incidence of wound bacterial and fungal contamination, invasive wound infection, and sepsis. Demographic data for the groups showed no differences in sex or total body surface area burned. Mortality and number of operative procedures and blood transfusions were not different between groups. Hospitalizations were longer in the delayed groups, which was associated with a higher incidence of significant wound contamination (P =.008). Invasive wound infection also increased significantly with delay of excision (P<.001). An increased incidence of sepsis was seen in patients with delayed wound excision and grafting (P =.04). Delays in excision were associated with longer hospitalization and delayed wound closure, as well as increased rates of invasive wound infection and sepsis. Our data indicate that early excision within 48 hours is optimal for pediatric patients with massive burns.