Biomedical subjects

Marc G Jeschke

Publications and source records attributed to Marc G Jeschke.

At least 37 records · Page 2Linked to original sources

PubMed2005

Identification of factors contributing to hepatomegaly in severely burned children.

Hepatomegaly is a common postmortem observation in severely burned children, with the liver often tripling in size when compared with normal livers for age, weight, and sex. Lesions identified at autopsy include deposition of large and small fat droplets in the hepatocyte, congestion, centrilobular necrosis, and cholestasis. The present study was designed to identify the primary causes of hepatomegaly in severely burned children postmortem. For this purpose, 41 autopsies were reviewed and, when available, blood and tissue samples were studied. Histopathologic findings showed that large intrahepatocytic fat droplets within hepatocytes and cholestasis were important contributors to hepatomegaly. Liver density and wet/dry weight ratios significantly decreased with increasing liver size. Hepatocyte volume increased with increasing liver size (P < 0.001) as did total fat content (P < 0.001). The liver enzymes, alanine aminotransferase and aspartate aminotransferase, remained normal except within 5 to 10 days of injury and 5 to 10 days of death. Triglycerides made up 4% to 70% of the total fat, with the percentage of triglycerides increasing with the severity of hepatomegaly. Saturated fatty acids represented about 85% of the total fatty acids in normal-sized livers, whereas in the largest livers (400% of predicted), only 25% of the fatty acids were saturated. This study provides evidence that 85% to 90% of the hepatomegaly observed in severely burned children postmortem is associated with hepatocyte enlargement, which includes up to 19% intracellular fat. Increases in extracellular protein, intracellular glycogen, and fluid accumulation may make a minor contribution to postburn hepatomegaly.

Age Factors↗

PubMed2005

Endogenous anabolic hormones and hypermetabolism: effect of trauma and gender differences.

OBJECTIVE: Protein degradation, negative nitrogen balance and compromised structure of essential organs have been associated with resistance and decreased production of anabolic hormones. In turn, increased levels of anabolic hormones are associated with improved survival. The aims of the present study were to determine the pattern of anabolic hormones, resting energy expenditure and cytokines in severely thermally injured pediatric patients and to compare these parameters in female and male patients. METHODS: Sixty-five children (1 to 16 years of age) sustaining a severe thermal injury (> or =40% TBSA) were included into the study. Patients were further divided into females (n = 22) and males (n = 43). Patient demographics, nutritional support, incidence of sepsis, inhalation injury, and mortality were noted. Resting energy expenditure was measured during hospital course by indirect calorimetry. Blood was drawn 0, 10, 20, and 40 days postburn and serum insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 and -3 (IGFBP-1, and -3), growth hormone, insulin, and cytokines were measured. RESULTS: There were no significant differences between females and males for demographics, nutritional intake, or concomitant injuries. In both groups, endogenous anabolic agents were drastically decreased by 3- to 5-fold up to 40 days posttrauma. Females had significantly higher levels of IGF-I, IGFBP-3, growth hormone, and insulin when compared with males, P < 0.05. Increased levels of anabolic hormones were associated with decreased stay on the ICU (females 36 +/- 22 days versus males 53+/- 39 days), decreased serum IL-1beta and TNF-alpha as well as resting energy expenditure, P < 0.05. CONCLUSION: Data indicate that despite adequate nutritional support, severe thermal injury leads to decreased anabolic hormones over a prolonged period of time. Female patients had significantly increased levels of anabolic hormones, which are associated with decreased proinflammatory mediators and hypermetabolism, leading to a significant shorter ICU stay compared with male patients.

Adolescent↗

PubMed2005

Metabolic and hormonal changes of severely burned children receiving long-term oxandrolone treatment.

OBJECTIVE: When given to children for 1 year after a severe burn, oxandrolone significantly improves lean body mass, bone mineral content, and muscle strength. The beneficial effects of oxandrolone on height and weight were observed 1 year after treatment was discontinued. To study the efficacy of oxandrolone in severely burned children for 12 months after burn and 12 months after the drug was discontinued. SUMMARY BACKGROUND DATA: Oxandrolone attenuates body catabolism during the acute phase after burn. It is unclear whether oxandrolone would have any beneficial effects during long-term treatment or if there were any effects after the drug was stopped. METHODS: Sixty-one children with 40% total body surface area burns were enrolled in this study. Patients were randomized into those to receive oxandrolone (n = 30) or placebo (n = 31) for the first 12 months. Treatment was discontinued after 12 months, and the patients were studied without the drug for the following 12 months. At discharge and 6, 12, 18, and 24 months after burn, height, weight, body composition, resting energy expenditure, muscle strength, and serum human growth hormone, insulin-like growth factor-I (IGF-1), IGF binding protein-3, insulin, cortisol, parathyroid hormone, tri-iodothyronine uptake (T3 uptake), and free thyroxine index (FTI) were measured. Statistical analysis used Tukey multiple comparison test. Significance was accepted at P < 0.05. RESULTS: Oxandrolone improved lean body mass, bone mineral content and muscle strength compared with controls during treatment, P < 0.05. Serum IGF-1, T3 uptake, and FTI were significantly higher during drug treatment compared with controls, P < 0.05. Significant increases in height and weight with oxandrolone were observed after the end of treatment. CONCLUSIONS: Oxandrolone improved body composition and strength in severely burned children during the 12 months of treatment. Its effect on height and weight continued after treatment was discontinued.

Adolescent↗

PubMed2005

Mortality related to gender, age, sepsis, and ethnicity in severely burned children.

Several studies have noted gender differences in adult mortality related to thermal injury, however, little is published on gender-related outcomes of burn patients 17 years of age or less. The aim of this study was to evaluate the relationships between mortality, gender, prepubertal and during puberty, ethnic origin, and age, with or without identified sepsis in severely burned children. Seven hundred forty-seven children admitted to our burn hospital from March 1985 to January 2005 with burns greater than 40% total body surface area were studied. Mortality associated with identified sepsis, gender, age, and ethnic origin were outcomes of interest. Two hundred sixty (35%) of the patients studied were girls and 487 (65%) were boys. No significant difference could be shown between girls and boys for the number of operations, time from burn to hospital admission, or the presence of identifiable inhalation injury. Nearly 60% of the male nonsurvivors and 48% of the female nonsurvivors in this study had identifiable sepsis at postmortem. The mortality rate was higher in infants and toddlers, age 0 to 2.9 years, compared with children and adolescents, age 3 to 17 years; however, there was no significant difference in rate of mortality between genders, prepuberty versus puberty, those with septic episodes, or ethnic origin. Burn mortality among infants and toddlers, children, and adolescents with greater than 40% total body surface area burns with or without identified sepsis could not be shown to be gender or ethnic origin dependent.

Adolescent↗

PubMed2004

Insulin attenuates the systemic inflammatory response in endotoxemic rats.

Insulin decreases the mortality and prevents the incidence of infection and sepsis in critically ill patients. The molecular and cellular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin on the inflammatory reaction during endotoxemia. Endotoxemic rats were randomly divided into two groups to receive either saline or insulin. The effects of insulin on hepatic signal transcription factor mRNA expression, proinflammatory and antiinflammatory cytokine mRNA and protein concentration were determined. Insulin administration did not change glucose or electrolyte levels, but significantly decreased proinflammatory signal transcription factors [CCAAT/enhancer-binding protein-beta, signal transducer and activator of transcription-3 and-5, RANTES (regulated on activation, normal T cell expressed and secreted)] and cytokine expression in the liver and serum levels of IL-1beta, IL-6, macrophage inflammatory factor, and TNFalpha. Insulin administration further decreased high mobility group 1 protein in the serum compared with controls. In addition, insulin increased antiinflammatory cytokine expression in the liver; serum levels of IL-2, IL-4, and IL-10; and hepatic suppressor of cytokine signaling-3 mRNA expression. Insulin modulates the inflammatory response by decreasing the proinflammatory and increasing the antiinflammatory cascade. Because glucose and electrolyte levels did not differ between insulin-treated patients and controls, we hypothesize that the effects are direct antiinflammatory mechanisms of insulin, rather than indirect, through modulation of glucose or electrolyte metabolism.

Animals↗

PubMed2004

Extended hypermetabolic response of the liver in severely burned pediatric patients.

HYPOTHESIS: The acute phase response is a cascade of events contributing to hypermetabolism and substrate catabolism. It was believed to persist for only a short time after injury. There is now evidence that systemic catabolism and hypermetabolism associated with thermal injury persevere for a long time. We hypothesize that the proinflammatory hepatic acute phase response perseveres for an extended time and enhances hypermetabolism longer than previously believed. DESIGN: Prospective study. SETTING: Intensive Care Burn Unit, Shriners Hospital for Children. PATIENTS: Twenty-three children (aged 1-16 years) sustaining a severe thermal injury (>/=40% total-body surface area) who remained in the intensive care unit longer than 30 days. MAIN OUTCOME MEASURES: Patient demographics, nutritional support, incidence of sepsis, inhalation injury, mortality, and levels of serum constitutive proteins, type I and type II acute phase proteins, free fatty acids, proinflammatory cytokines, insulin-like growth factor (IGF) I, IGF binding protein-1, IGF binding protein-3, and hepatocyte growth factor. RESULTS: After thermal injury, constitutive hepatic protein levels decreased 2- to 3-fold 80 days after burn, whereas acute phase protein levels increased. Free fatty acid levels were increased 5 days after burn. Proinflammatory cytokine levels (interleukin [IL] 1, IL-6, IL-8, IL-10, and tumor necrosis factor) and IGF binding protein-1 levels were elevated for 40 days after burn, whereas serum IGF-I and IGF binding protein-3 levels were decreased. Hepatocyte growth factor levels were increased immediately after burn but rapidly returned to the normal range. CONCLUSIONS: Despite adequate nutritional support, a severe thermal injury induces the proinflammatory acute phase response for a prolonged period. Thus, the liver with the hepatic acute phase response plays a more important role during catabolism after burn than previously believed. Pharmacologic agents that improve hepatic function may be an effective approach to attenuate hypermetabolism after trauma.

Acute-Phase Reaction↗

PubMed2004

Applied tissue engineering in the closure of severe burns and chronic wounds using cultured human autologous keratinocytes in a natural fibrin matrix.

Whereas in severe burns cultured human epithelial cells may well serve as a life saving method, the true value of tissue-engineered skin products in chronic wound care has yet to be clearly defined. Among other well-known clinical problems, the engraftment rate of commercially available multilayered "sheet grafts" has been shown to vary extremely. Adherence of transplanted cells to the wound bed--especially in the presence of potential wound contamination-- is one of the crucial aspects of this technique. Keratinocyte suspensions in a natural fibrin sealant matrix can potentially treat a variety of skin defects. In acute burn wounds, as well as in chronic wounds the clinical application of this type of tissue-engineered skin substitute demonstrates the capacity of cultured human autologous keratinocytes in a fibrin sealant matrix to adhere to wound beds, attach and spread over the wound resulting in reepithelialization of both acute and chronic wounds. In full thickness burns the combination of this new tool with allogenic dermis is a promising option to achieve complete dermal-epidermal reconstitution by means of tissue engineering and guided tissue repair. When transferring this technique into the treatment of chronic wounds we found an optimal preparation of such recipient wound beds to be crucial to the success. The additional application of continuous negative pressure (vacuum therapy) and preliminary chip skin grafting to optimally prepare the recipient site may be helpful tools to achieve such well-prepared and graftable surfaces. Prospective controlled comparative studies should be designed to further assess the clinical efficacy of this technique.

Burns↗

PubMed2004

Development of new reconstructive techniques: use of Integra in combination with fibrin glue and negative-pressure therapy for reconstruction of acute and chronic wounds.

Large wounds resulting from severe injuries are generally treated with extended reconstructive operations (e.g., free flaps), which are accompanied by long hospitalizations and risks of infection, thrombosis, and flap loss. Integra is a collagen template that can be used for reconstruction of defects. The take rate and the rate of infection are essential for the successful use of Integra (Johnson and Johnson, Hamburg, Germany). Whether the take rate and integration of Integra could be improved with the use of fibrin glue and negative-pressure therapy was assessed. Between January of 2002 and December of 2002, patients with large defects who underwent Integra grafting for reconstruction were randomly divided into groups receiving either a new treatment with fibrin glue-anchored Integra and postoperative negative-pressure therapy or conventional treatment. Demographic features, cause of the wound, location of the wound, take rate, complications of Integra coverage, time from Integra coverage to skin transplantation, and functional and aesthetic results were assessed. Twelve patients (with similar group distributions with respect to sex, age, and location and cause of the injury) were included in the study. The take rate was 78 +/- 8 percent in the conventional treatment group and 98 +/- 2 percent in the fibrin/negative-pressure therapy group (p < 0.003). The mean period from Integra coverage to skin transplantation was 24 +/- 3 days in the conventional treatment group but only 10 +/- 1 days in the fibrin/negative-pressure therapy group (p < 0.002). The decrease in the interval between coverage with Integra and skin transplantation resulted in shorter hospital stays. The use of fibrin glue and negative-pressure therapy in combination with Integra could shorten the period from coverage to integration, which would be beneficial in terms of decreased risks of infection, thrombosis, and catabolism. Therefore, it is suggested that Integra be used in combination with fibrin glue and negative-pressure therapy to improve clinical outcomes and shorten hospital stays, with decreased risks of accompanying complications.

Adult↗

PubMed2004

Insulin treatment improves the systemic inflammatory reaction to severe trauma.

OBJECTIVE: Determine the effect of insulin on the systemic inflammatory response, pro- and anti-inflammatory cytokines and hepatic acute-phase-response in severely burned pediatric patients. SUMMARY BACKGROUND DATA: The systemic inflammatory and hepatic acute-phase-response contribute to hypermetabolism, multi-organ failure, and mortality. Insulin has been recently shown to decrease mortality and to prevent the incidence of multi-organ failure in critically ill patients; however, the underlying mechanisms have not been defined. METHODS: Thirteen thermally injured children received insulin to maintain blood glucose at a range from 120 to 180 mg/dl, 15 children received no insulin with blood glucose levels also at range from 120 to 180 mg/dl and served as controls. Our outcome measures encompassed the effect of insulin on pro-inflammatory mediators, the hepatic acute-phase-response, fat, and the IGF-I system. RESULTS: Insulin administration decreased pro-inflammatory cytokines and proteins, while increasing constitutive-hepatic proteins (P < 0.05). Burned children receiving insulin required significantly less albumin substitution to maintain normal levels compared with control (P < 0.05). Insulin decreased free fatty acids and serum triglycerides when compared with controls (P < 0.05). Serum IGF-I and IGFBP-3 significantly increased with insulin administration (P < 0.05). CONCLUSION: Insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.

Acute-Phase Reaction↗

PubMed2004

Insulin treatment improves hepatic morphology and function through modulation of hepatic signals after severe trauma.

OBJECTIVE: The purpose of the present study was to determine the effect of insulin therapy on hepatic function, structure, and hepatic mRNA and protein cytokine expression during the hypermetabolic cascade post burn. SUMMARY BACKGROUND DATA: Liver function and morphology are crucial for survival of patients suffering from trauma, operations, or infections. Insulin decreased mortality and prevented the incidence of multiorgan failure in critically ill patients. METHODS: Rats received a thermal injury and were randomly divided into the insulin or control group. Our outcome measures encompassed the effect of insulin on hepatic proteins, hepatic pro- and anti-inflammatory cytokines mRNA and proteins, hepatocyte proliferation, including Bcl-2 and hepatocyte apoptosis, with caspases-3 and caspases-9. RESULTS: Insulin significantly improved hepatic protein synthesis by increasing albumin and decreasing c-reactive protein and fat (P < 0.05). Insulin decreased the hepatic inflammatory response signal cascade by decreasing hepatic pro-inflammatory cytokines mRNA and proteins IL-1beta and tumor necrosis factor at pretranslational levels. Insulin increased hepatic cytokine mRNA and protein expression of IL-2 and IL-10 at a pretranslational level when compared with controls (P < 0.05). Insulin increased hepatocyte proliferation along with Bcl-2 concentration, while decreasing hepatocyte apoptosis along with decreased caspases-3 and -9 concentration, thus improving liver morphology (P < 0.05). CONCLUSIONS: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring hepatic homeostasis, which has been shown to be critical for organ function and survival of critically ill patients.

Animals↗

PubMed2004

Exogenous liposomal IGF-I cDNA gene transfer leads to endogenous cellular and physiological responses in an acute wound.

The purpose of the present study was to examine whether exogenous liposomal cDNA gene transfer is recognized by the cell and causes endogenous cellular and physiological responses. When administered as a protein, IGF-I is known to cause adverse side effects due to lack of cellular responses. Therefore, we used IGF-I cDNA as a vector to study cellular and physiological effects after liposomal administration to wounded skin. Sprague-Dawley rats were given a scald burn to inflict an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.2 microg vehicle) or liposomes plus the IGF-I cDNA (2.2 microg) and Lac Z gene (0.22 microg). Transfection was confirmed by histochemical assays for beta-galactosidase. Planimetry, immunological assays, and histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, and dermal and epidermal regeneration. IGF-I cDNA transfer increased IGF-I protein expression and caused concomitant cellular responses by increasing IGF binding protein (IGFBP)-3 and decreasing IGFBP-1. IGF-I cDNA gene transfer increased keratinocyte growth factor expression and exerted promitogenic antiapoptotic effects on basal keratinocytes, thus improving epidermal regeneration. IGF-I cDNA improved dermal regeneration by an increased collagen deposition and morphology. IGF-I cDNA increased VEGF concentrations and thus neovascularization. Exogenous-administered IGF-I cDNA is recognized by the cell and leads to similar intracellular responses as the endogenous gene. Liposomal IGF-I gene transfer further leads to improved dermal and epidermal regeneration by interacting with other growth factors.

Animals↗

PubMed2004

Effect of growth factors as therapeutic drugs on hepatic metabolism during the systemic inflammatory response syndrome.

Characteristic for critically ill patients is a hypermetabolism and catabolism that is associated with impairment of the structure and function of essential organs, such as the immune system, kidney, peripheral muscles and the liver. The liver-gut-axis, with liver integrity, metabolism and function are crucial for survival of patients suffering from trauma, operations or infections. The hepatic acute phase response represents a cascade of events characterized by the upregulation of acute phase proteins and the downregulation of constitutive hepatic proteins. The goal of the hepatic acute-phase-response, which is mediated by cytokines and signal transcription factors, is to restore homeostasis. However, multiple studies have shown that a sustained or increased acute phase response is detrimental with the uncontrolled and prolonged action of acute phase proteins. The downregulation of constitutive hepatic proteins may further augment these detrimental effects. Research has focused on the attenuation of the inflammatory response using anti-inflammatory agents or antibodies against pro-inflammatory cytokines such as tumor necrosis (TNF), interleukin-1beta (IL-1beta), or their receptors. These approaches showed promising results in vitro and in animal models; however, when these approaches entered clinical trials it became evident that these promising animal data could not be substantiated in humans. A different approach is to attenuate the inflammatory cascade by the administration of growth factors. Growth factors exert anabolic effects and affect the inflammatory hepatic metabolism. The present review discusses the effect of recombinant human growth hormone, insulin-like growth factor-I, hepatocyte growth factor and insulin on the hepatic metabolism and homeostasis during inflammation and delineates the therapeutic benefit and limitation of growth factor administration in critically ill patients.

Acute-Phase Reaction↗

PubMed2003

Effects of incremental starvation on gut mucosa.

Starvation induces gut mucosal atrophy, but the effects of progressive dietary restriction are not defined. The study's purpose was to determine the effects of incremental starvation on gut epithelial cell turnover. After food intake of mice was determined, they were divided into five groups: control (ad libitum fed), 75% normal intake, 50% intake, 25% intake, and fasted. Mice were killed after 48 hours, and the proximal small bowel were assessed for weight and protein content. Histologic specimens were examined for villus morphology, apoptosis, and proliferation. After 48 hr of diet restriction, bowel weight decreased in the 50% intake, 25% intake, and fasted groups. Villus density also decreased in the fasted group. Proliferation progressively decreased in the diet-restricted groups. Apoptosis increased in the fasted group, primarily in the villus tip. In conclusion, incremental starvation produces progressive small bowel atrophy. The mechanism involves both decreased gut epithelial cell proliferation and increased apoptosis.

Animals↗

PubMed2003

Differences in the hepatic signal transcription pathway and cytokine expression between thermal injury and sepsis.

Inflammation and catabolism in response to trauma, surgery, critical illness or bacteria lead to a compromise of essential organs, which can lead to prolonged clinical stay and even death. Mediators responsible for catabolism were thought to be proinflammatory cytokines, but recently the focus has shifted to signal transduction. The purpose of the present study was to determine differences between two pathophysiologic states, sepsis and thermal injury, in signal transduction and cytokine expression and thus define the importance of the signal transcription pathway. Rats were randomly divided to either receive lipopolysaccharide (3 mg/kg body weight or a 30% total body surface area burn) or they received no treatment and served as controls. Animals were sacrificed 1, 2, 5, and 7 days postinsult and serum and liver harvested for analysis. A thermal injury appeared to have a slow release and expression of signal transcription factors and cytokines and a sepsis showed a rapid increase of mediators and also a fast decrease. The changes in cytokine profiles after burn, particularly interleukin-1beta and macrophage inhibitory factor, appear to be mediated by C/EBP-beta and STAT-3, whereas after the induction of a sepsis, tumor necrosis factor and interleukin-6 are mainly mediated by STAT-5. Based on our findings we suggest that the pathophysiologic state of a thermal injury is not comparable with sepsis in association with signal transcription factors and the differences in intracellular and extracellular signaling therefore opens new ideas for therapeutic options.

Animals↗

PubMed2002

Modulation of types I and II acute phase reactants with insulin-like growth factor-1/binding protein-3 complex in severely burned children.

OBJECTIVE: To determine whether 0.5 mg/kg insulin-like growth factor (IGF)-1/binding protein (IGFBP)-3, given intravenously, effectively alters the acute phase response in severely burned children. DESIGN: Longitudinal trial with each patient serving as their own control. SETTING: University-affiliated pediatric bum center. PATIENTS: Nine children, 15 yrs of age or less, with burns covering >40% of the total body surface area. INTERVENTIONS: Standard burn care with early burn wound excision and grafting. Blood sampled at defined time points before and after operative procedures. MEASUREMENTS AND RESULTS: Determination of types I and II acute phase reactant proteins, constitutive serum proteins, serum cytokines, serum IGF-1, IGFBP-3, and growth hormone levels. Treatment with IGF-1/BP-3 attenuated increases in type I (complement 3, alpha1-acidglycoprotein) and type II (haptoglobin, alpha1-antitrypsin) acute phase proteins. Further, IGF-1/BP-3 increased constitutive serum protein levels (prealbumin, retinol binding protein, transferrin) and decreased serum IL-6 levels. CONCLUSIONS: Low-dose IGF-1/BP-3 effectively attenuated the type I and type II hepatic acute phase response, increased serum levels of constitutive proteins, and modulated the hypermetabolic response.

Acute-Phase Proteins↗

PubMed2002

Cleland's ligaments: an anatomic study.

The anatomy and function of Cleland's ligaments--thought by the authors to require clarification because of the conflicting anatomic descriptions in the literature--are reviewed. A statistical representation of the structure of these ligamentous bundles was derived from the study of 16 fixed human cadaveric digits and five fresh cadaveric digits, all from different patients. The results demonstrate a large variation in anatomy. However, this anatomic heterogeneity is not indicative of an equally varied function. In general, it was found that the majority of Cleland's ligaments traversed a great distance adherent to the skin before actually inserting in the dermis. Over one-third of the dorsal fibers demonstrated a multiplanar organization, fanning out before inserting into the skin. In contrast, the ventral fibers did not fan out before inserting into the skin. Excision of these ventral fibers revealed a separate "ledgelike" plane of fibers arising from the fibrous flexor sheath and running in a straight line perpendicular to the long axis of the digit. A branch of the digital nerve was found to pierce this ligamentous layer in the majority of digits studied. Unlike those of previous reports, the results of the present study suggest that the ligaments have a constant function of anchoring the skin of the digit on both the dorsal and ventral aspects, thereby preventing the displacement of skin during flexion of the digits. All previous studies failed to make this conclusion. The anatomic relationship to the digital neurovascular bundle also suggests that Cleland's ligaments may stabilize the digital vessels during flexion. In conclusion, Cleland's ligaments are highly functional structures and are essential for normal cutaneous stability during digital movements.

Female↗

PubMed2002

IGF-I/IGFBP-3 equilibrates ratios of pro- to anti-inflammatory cytokines, which are predictors for organ function in severely burned pediatric patients.

BACKGROUND: We hypothesized that ratios of pro- to anti-inflammatory cytokines can be associated with hepatic, cardiac, and renal function after a severe trauma and can be used as predictors for clinical outcome. Furthermore, insulin-like growth factor-I (IGF-I) in combination with its principle binding protein (IGFBP-3) equilibrates pro- to anti-inflammatory cytokine ratios and improves homeostasis of severely burned pediatric patients. MATERIALS AND METHODS: Seventeen severely burned children were given a continuous infusion of IGF-I/BP-3 for 5 days after wound excision and grafting; seven were given saline during the same time period to serve as controls. Patient demographics and mortality were determined. Five days after excision and grafting, cardiac function was determined and blood samples were taken for serum levels of IGF-I, IGFBP-3, creatinine, pre-albumin, cholinesterase, pro-inflammatory cytokines (IL-1beta, IL-6, and TNF), and anti-inflammatory cytokines (IL-2, IL-4, IL-10 and IFN-gamma). RESULTS: There were no differences between IGF-I/BP-3 and controls in age, gender, burn size, or mortality. Serum IGF-I in burned children given the IGF-I/BP-3 complex increased from 102 + 15 to 433 + 33 microg/ml and IGFBP-3 increased from 1.5 + 0.2 to 3.0 + 0.2 microg/ml (p < 0.05). Serum pre-albumin and cholinesterase increased with IGF-I/BP-3, whereas serum creatinine decreased when compared to controls (p < 0.05). IGF-I/BP-3 increased cardiac index by 16% and stroke volume index by 15% (p < 0.05). These improvements in organ homeostasis were associated with decreased ratios of pro- to anti-inflammatory cytokines in the IGF-I/BP-3 group when compared to controls (p < 0.05). CONCLUSIONS: Increased ratios of pro- to anti-inflammatory cytokines may indicate a higher risk for the incidence of multi-organ failure. We therefore suggest that ratios of pro-inflammatory to anti-inflammatory cytokines can be used to predict organ function. We further conclude that IGF-I/BP-3 equilibrates the balance between pro- and anti-inflammatory cytokines, which was associated with improved cardiac, renal, and hepatic function. The benefit of IGF-I/BP-3 in ameliorating the inflammatory response may also apply in reducing the multi-organ failure often observed in the state of severe trauma.

Adolescent↗

PubMed2002

Insulin attenuates the systemic inflammatory response to thermal trauma.

BACKGROUND: Insulin has been recently shown to decrease mortality and prevent the incidence of multi-organ failure in critically ill patients. The molecular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin therapy on the systemic inflammatory response. In vivo we determined the effect of insulin therapy on the inflammatory cascade, which was induced by thermal injury. MATERIALS AND METHODS: Thermally injured rats (30% TBSA) were randomly divided into two groups to receive either saline (n= 28) or insulin (n= 28). Our outcome measures encompassed the effect of insulin on pro- inflammatory cytokines, anti-inflammatory cytokines, and hepatic signal transcription factor mRNA expression. RESULTS: Insulin significantly decreased dose dependently serum pro-inflammatory cytokines IL-1beta at 1, 5, and 7 days, IL-6 at 1 day, MIF at 5 and 7 days, and TNF at 1 and 2 days after injury when compared with controls (p<0.05). Insulin increased anti-inflammatory cytokines IL-2 and IL-4 at 5 and 7 days after trauma, and IL-10 at 2, 5 and 7 days after trauma when compared with controls (p< 0.05). Pro-inflammatory signal transcription factors STAT-5 and C/EBP-beta mRNA were significantly decreased 1 and 2 days posttrauma; insulin increased anti-inflammatory signal transcription factor mRNA expression of SOCS-3 and RANTES 7 days after the injury (p< 0.05). CONCLUSIONS: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro- inflammatory and increasing the anti-inflammatory cas-cade, thereby restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.

Animals↗