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Biomedical subjects

Rene Przkora

Publications and source records attributed to Rene Przkora.

16 recordsLinked to original sources

Blood transfusions are associated with increased risk for development of sepsis in severely burned pediatric patients.

OBJECTIVE: To determine the risk of developing sepsis following transfusion of blood products in severely burned pediatric patients. DESIGN: Retrospective, cohort study. SETTING: Shriners Hospital for Children and University Hospital. PATIENTS: Severely burned pediatric patients with >30% total body surface area (TBSA) burn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-seven pediatric burn patients over a period of 7 yrs (1997-2004) were included in the study, with 25 patients being septic at admission and therefore excluded. Patients were stratified according to TBSA burn and presence or absence of inhalation injury. The amounts of packed red blood cells (RBCs) and fresh frozen plasma (FFP) were recorded during hospital stay before the development of sepsis. Blood product administration was normalized for the number of surgeries and divided into two groups: high (RBCs>20/FFP>5) or low (RBCs<20/FFP<5) amount of blood products. Sepsis was diagnosed based on the criteria set by the Society of Critical Care Medicine in conjunction with positive blood culture or presence of organisms in the organs at autopsy. By stratifying the groups into low and high blood transfusion, we found that patients with >60% TBSA burn with inhalation injury have an 8% risk of developing sepsis in the low RBC group, which increases to 58% in the high RBC group (p<.05). Similar results were found for RBCs per operation, FFP, and FFP per operation (p<.05). There were no differences in age and gender between groups. CONCLUSIONS: Pediatric burn suffering from a 60% TBSA burn with concomitant inhalation injury are more likely to develop sepsis if they are given high amounts of blood products, indicating an immunocompromised state following blood transfusion.

Burns↗

Insulin attenuates the cytokine response in a burn wound infection model.

A massive burn is one of the most serious injuries resulting in major imbalances of the immune system. The aftermath of a burn is frequently complicated by infections and septic events that additionally increase mortality and morbidity. The aim of the present study was to investigate if insulin attenuates the cytokine response of burned mice challenged with Pseudomonas. Male mice (C57/BL/6) received a full thickness burn of 35% of their total body surface area. Mice received 5 IU/kg insulin i.p. or an equal volume of saline for 5 days after burn. Mice were challenged with 5x10 colony forming units Pseudomonas aeruginosa intraperitoneally. Serum was harvested 6 h after the bacterial challenge, and 18 serum cytokines were measured using the Bio-Plex suspension array system (Bio-Rad, Hercules, Calif). All 18 cytokines were elevated after the Pseudomonas challenge. However, mice treated with insulin showed significantly lower proinflammatory cytokine concentrations of interleukin 5, interleukin 6, and keratinocyte-derived chemokine after the Pseudomonas infection when compared with placebo-treated mice (P<0.05). In contrast, serum concentrations of G-CSF were significantly higher in insulin-treated animals when compared with placebo (P<0.05). We conclude, that insulin treatment selectively modulates specific cytokines in a burn wound infection model.

Animals↗

The effects of oxandrolone and exercise on muscle mass and function in children with severe burns.

OBJECTIVES: Severe burns are associated with a significant loss of muscle and strength. Studies have reported that oxandrolone improves lean body mass in muscle-wasting conditions. Also shown previously in burned children is that an exercise program increases lean body mass and muscle strength. We hypothesized that oxandrolone, in combination with exercise, would increase lean body mass and muscle strength in severely burned children more than oxandrolone alone or exercise alone. METHODS AND PATIENTS: Fifty-one burned children (> or = 40% total body surface area burned) were randomly assigned to receive oxandrolone alone (0.1 mg/kg per day orally; n = 9), oxandrolone and exercise (n = 14), placebo and no exercise (n = 11), or placebo and exercise (n = 17). Administration of oxandrolone was started at discharge and continued until 1 year after burn. The 12-week exercise training program was started 6 months after burn. Serum hormones, lean body mass, muscle strength, and peak cardiopulmonary capacity were assessed at 6 (baseline) and 9 months after burn. Data were analyzed using a 1-way analysis of variance, and significance was set at P < .05. RESULTS: The mean percentage of change or increase in weight and lean body mass in the oxandrolone and exercise group was significant compared with placebo and exercise, as well as with the oxandrolone alone group or placebo and no exercise group. Furthermore, lean body mass was significantly improved in the oxandrolone and exercise, oxandrolone alone, and placebo and exercise group compared with the group only receiving placebo. Muscle strength significantly increased in oxandrolone and exercise, placebo and exercise, and the oxandrolone alone group when compared with the placebo and no exercise group. The peak cardiopulmonary capacity was significantly higher in both exercise groups. Insulin-like growth factor 1 was significantly increased in the oxandrolone alone group compared with placebo and exercise and placebo and no exercise. Both exercise groups showed significant changes in insulin-like binding-protein-3 when compared with groups without exercise. CONCLUSIONS: Oxandrolone, in combination with exercise, is beneficial in severely burned children, thus improving their rehabilitation.

Adolescent↗

Gut mucosal homeostasis and cellular mediators after severe thermal trauma and the effect of insulin-like growth factor-I in combination with insulin-like growth factor binding protein-3.

Increased small bowel epithelial cell apoptosis and decreased cell proliferation lead to impairment of gut mucosal integrity and function after thermal injury. Impairment of gut integrity is associated with increased bacterial translocation and incidence of sepsis. The purpose of this study was to determine whether IGF-I/IGF binding protein (IGFBP)-3 can improve small bowel homeostasis after injury and by which cellular mechanisms these changes occur and to identify changes in apoptosis-related genes after burn and the effect of bile acid on small bowel epithelial cell apoptosis after burn. Rats sustained a thermal injury and received saline or the IGF-I/IGFBP-3 complex. Serum and small intestine were taken at 1, 2, 5, and 7 d after injury and serum inflammatory cytokines and mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators were measured. Apoptosis-related gene expression and the bile acid pool were determined in separate experiments up to 6 h after burn. Gut epithelial cell apoptosis as well as apoptosis-related genes were increased after the thermal injury, whereas bile acid secretion was significantly decreased (P < 0.05). IGF-I/IGFBP-3 significantly improved villous height and cells per villous by decreasing small bowel epithelial cell apoptosis and increasing proliferation (P < 0.05). Decreased apoptosis was associated with decreased Fas, Fas-ligand, and TNF when compared with saline (P < 0.05). A severe thermal injury caused an up-regulation of apoptosis and apoptosis-related genes and down-regulation of bile acid secretion. IGF-I/IGFBP-3 decreases small bowel epithelial cell apoptosis through down-regulation of the Fas pathway, which improves gut mucosal integrity after a severe thermal injury.

Animals↗

Temporary vertical transarticular-pin fixation of unstable ankle fractures with critical soft tissue conditions.

Unstable ankle fractures are demanding injuries to treat. Open reduction and internal fixation are accepted as standard care, however, in patients with severe soft tissue damage or serious medical conditions, this approach may not always be advisable. Closed reduction with temporary fixation using vertical transarticular pins is one method to maintain joint alignment until an open technique is possible. Fourteen patients (median age: 59.5 years) with unstable ankle fractures, including three type-2 open fractures, were included in the study. Open reduction and fixation was delayed because of severe soft tissue damage, and a temporary transarticular pin fixation using two Kirschner wires was performed. After a median of 8.4 days, an open reduction and internal fixation was carried out in all patients. No complications related to the temporary arthrodesis were observed during the acute phase, and follow-up at 24 months revealed no damage to the articular surface attributable to the pin insertion. The median Olerud-score was 33.43, but three patients showed signs of early post-traumatic arthritis which we felt were due to the initial fracture. We conclude that closed reduction and temporary fixation using vertical transarticular pins of unstable ankle fractures is a safe method of maintaining joint alignment until a definitive open approach is feasible.

Adult↗

Cytokine expression profile over time in severely burned pediatric patients.

A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structure of essential organs. The massive release of cytokines is implicated in this hypermetabolic response. The aim of the present study was to compare cytokine expression profiles from severely burned children without signs of infections or inhalation injury (n = 19) to the cytokine profiles from normal, noninfected, nonburned children (n = 14). The Bio-Plex suspension array system was used to measure the concentration of 17 cytokines. The expression of proinflammatory and anti-inflammatory cytokines was maximal during the first week after thermal injury. Significant increases were measured for 15 mediators during the first week after thermal injury: interleukin (IL) 1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 p70, IL-13, IL-17, interferon gamma, monocyte chemoattractant protein 1, macrophage inflammatory protein 1beta, and granulocyte colony-stimulating factor (P < 0.05). Granulocyte-macrophage colony-stimulating factor was significantly increased during the second week after burn (P < 0.05). Within 5 weeks, the serum concentrations of most cytokines decreased, approaching normal levels. When compared with the cytokine levels measured in normal children, a total of 16 cytokines were significantly altered (P < 0.05). After severe burn, a specific cytokine expression profile is observed in patients without complications such as inhalation injury or sepsis. The cytokine concentrations decrease during 5 weeks after burn but remain elevated over nonburned values. Furthermore, the elevation in most serum cytokine levels during the first week after burn may indicate a potential window of opportunity for therapeutic intervention.

Adolescent↗

Beneficial effects of extended growth hormone treatment after hospital discharge in pediatric burn patients.

OBJECTIVE: To study the efficacy of growth hormone given to severely burned children from discharge to 12 months after burn and for 12 months after the drug was discontinued. SUMMARY BACKGROUND DATA: We have previously shown that low-dose recombinant human growth hormone (rhGH), given to children after a severe thermal injury, successfully improved lean muscle mass, bone mineral content, and growth. The aim of the present study was to investigate long-term functional improvements after treatment. METHODS: Forty-four pediatric patients with over 40% total body surface area burns were studied for 24 months after burn. Patients were randomized to receive either rhGH (0.05 mg/kg body weight) or placebo. Height, weight, body composition, serum hormones, resting energy expenditure, cardiac function, muscle strength, and number of reconstructive procedures performed were measured during rhGH treatment and for 12 months after treatment was discontinued. Statistical analysis used Tukey's multiple comparison test. Significance was accepted at P < 0.05. RESULTS: Height, weight, lean body mass, bone mineral content, cardiac function, and muscle strength significantly improved during rhGH treatment compared with placebo (P < 0.05). This treatment significantly increased GH, IGF-I, and IGFBP-3, whereas serum cortisol decreased (P < 0.05). The number of operative reconstructive procedures was significantly lower with rhGH (P < 0.05). Improvements in height, bone mineral content, and IGF-1 concentrations persisted after rhGH treatment (P < 0.05). No side effects with rhGH were observed. CONCLUSIONS: Administration of rhGH for 1 year after burn was safe and improved recovery. These salutary effects continued after rhGH treatment was discontinued.

Burns↗

Body composition changes with time in pediatric burn patients.

BACKGROUND: Major trauma and burns are associated with whole body catabolism which can persist for 1 or more years after injury. This study investigates body composition in massively burned children for up to 2 years. METHODS: Twenty-five pediatric patients with greater than 40% total body surface area burns were studied. At discharge, 6, 12, 18, and 24 months after burn height, weight, body composition, resting energy expenditure (REE), serum growth hormone, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), insulin, cortisol, parathyroid hormone, and thyroid hormones were measured. Tukey's test was used for analysis. Significance was accepted at p < 0.05. RESULTS: Lean body mass, fat mass, bone mineral content, height, and weight increased significantly during the second year after burn. Percent predicted REE decreased significantly, whereas IGFBP-3 and parathyroid hormone levels increased significantly over time. Insulin and T3 uptake were significantly higher at discharge. CONCLUSIONS: Body composition of severely burned children significantly improved in the second year compared with the first year after injury. This demonstrates a need for long-term rehabilitation in these burn patients.

Absorptiometry, Photon↗

Ganglioneuroma : primary tumor or maturation of a suspected neuroblastoma?

Ganglioneuroma is a benign neurogenic tumor. These tumors are originating from neuroepithelium along sympathetic ganglia. Main localization is the mediastinum in children older than 10 years. An association with malignant neuroblastoma is rarely observed and it still remains a topic under current discussion. We describe the clinical course of a 17 year-old female patient with a large presacral mass causing amenorrhoea and weight loss. Eleven years before presentation, an incidental urine test showed an elevation of vanillylmandelic acid (VMA) and homovanillic acid (HMA) and a neuroblastoma was suspected. However, further investigations showed no tumor and the test results turned out to be normal within 1 year. Now, a malignant neurogenic tumor was again suspected, but a CT-guided biopsy revealed a benign tumor. The mass was originating from the left sacral nerve roots. A tumor resection via a dorsal approach was performed. Final histology showed a differentiated ganglioneuroma. This is, to our knowledge, the first report describing a patient with elevated VMA/HMA and suspected neuroblastoma who developed a ganglioneuroma 11 years later. The association of ganglioneuroma and neuroblastoma and the abnormal urine tests pointing toward a neuroblastoma 11 years ago remains unclear and the possible answers are discussed in our report.

Adolescent↗

The effect of growth hormone on gut mucosal homeostasis and cellular mediators after severe trauma.

BACKGROUND: Gut mucosal integrity and function is impaired after severe trauma with associated increases in small bowel epithelial cell apoptosis and decreases in cell proliferation. Growth hormone improves gastrointestinal function during chemotherapy and has anabolic effects on protein synthesis. The purpose of this study was to determine whether growth hormone can improve small bowel homeostasis after injury and by which cellular mechanisms these changes occur. MATERIALS AND METHODS: Rats were pair-fed, given a thermal trauma, and received saline (n = 28) or GH (2.5 mg/kg every 24 h, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, apoptotic, and proliferative mediators, such as Caspases-3, -8, Fas and Fas-Ligand, Bcl-2, and Bcl-x. In addition serum cytokines were determined. RESULTS: Gut epithelial cell apoptosis and proliferation were increased in both groups after the thermal injury (P < 0.05). GH had neither an effect on small bowel epithelial cell apoptosis or proliferation, nor dependent cellular mediators after thermal injury. However, GH significantly improved villous morphology (height and cell number) when compared with controls (P < 0.05). RhGH was found to significantly increase serum TNF-alpha compared to controls (P < 0.05). CONCLUSION: Growth hormone improves small bowel homeostasis after severe trauma independent from small bowel epithelial cell apoptosis or proliferation, probably by increasing the life span.

Animals↗

The effect of hepatocyte growth factor on gut mucosal apoptosis and proliferation, and cellular mediators after severe trauma.

BACKGROUND: A severe burn injury is associated with an impairment of gut mucosal integrity and function, which is due to increases in small-bowel epithelial cell apoptosis and decreases in cell proliferation. Hepatocyte growth factor (HGF) was shown to improve regeneration in the liver, mesentery, and skin. The purpose of this study was to determine whether HGF can improve small-bowel homeostasis after injury and the cellular mechanisms by which these changes occur. METHODS: Rats were pair-fed, underwent thermal trauma, and received saline (0.9% NaCl; n = 28) or HGF (200 microg/kg iv every 12 hours, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators, such as caspase-3 and caspase-7, Fas and Fas-ligand, Bcl-2, and Bax. In addition, serum cytokines were determined. RESULTS: Gut epithelial cell apoptosis was increased in the saline and HGF groups after the thermal injury. Despite an increase in serum tumor necrosis factor-alpha and interleukin-1beta, HGF did not affect small-bowel cell apoptosis, but it improved proliferation at days 1 and 2 after injury, which was associated with increased villous height and cell per villous, compared with saline controls, P < .05. Increased mucosal cell proliferation was associated with increased Bcl-2 in the HGF group, P < .05. HGF had no effect on apoptotic mediators, such as Fas, Fas-L, or caspase-3 and caspase-7. CONCLUSIONS: HGF improves small-bowel morphology after a severe burn by increasing mucosal Bcl-2 and, concomitantly, small-bowel epithelial cell proliferation.

Animals↗

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↗

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↗

Synovial sarcoma--unusual presentation with cerebral hemorrhage.

INTRODUCTION: Soft-tissue sarcomas account for 1% of all malignancies in adults. Typical symptoms comprise a growing and painless mass. Occasionally, the diagnosis is facilitated by secondaries. MATERIALS AND METHODS: Here we report the first case presented with intracranial hemorrhage caused by a metastasis of a previously unknown synovial sarcoma. The 74-year-old female patient was under anticoagulation for recurrent thrombosis of the right popliteal vein due to compression by the sarcoma, misdiagnosed as Baker's cyst. The brain metastasis was resected, and after an incisional biopsy of the suspected tumor, which confirmed the diagnosis of a synovial sarcoma, an above knee amputation was performed because of the invasion of the neurovascular structures in the popliteal fossa. RESULTS: The patient died 11 months after the initial event from pulmonary and further brain metastases. CONCLUSION: Brain metastases are seldom the primary factor in the management of advanced synovial sarcoma. Initially, the primary tumor was thought to be a benign cyst; we therefore recommend a biopsy/excision of lesions greater than 5 cm in size and with growth tendency to allow appropriate treatment.

Aged↗

Interaction of exogenous liposomal insulin-like growth factor-I cDNA gene transfer with growth factors on collagen expression in acute wounds.

Growth factors have been shown to modulate the complex cascade of wound healing, however, interaction between different growth factors during dermal and epidermal regeneration is still not entirely defined. We have recently shown that exogenous liposomal gene transfer of cDNA results in physiologic expression and response in an acute wound. In the present study we determined the interaction between insulin-like growth factor-I (IGF-I), a mesenchymal growth factor, administered as liposomal cDNA, with other dermal and epidermal growth factors on collagen synthesis in an acute wound. Sprague-Dawley rats were given a scald burn to inflict an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus a beta-galactosidase containing plasmid (Lac Z [0.2 microg, vehicle]), or liposomes plus the IGF-I cDNA containing plasmid (2.2 microg) and Lac Z (0.2 microg). Immunological assays, histological and immunohistochemical techniques were used to determine growth factor concentration and different types of collagen (I, III, and IV) after IGF-I cDNA gene transfer. IGF-I cDNA transfer accelerated reepithelization and was associated with increased levels of IGF-I, fibroblast growth factor, keratinocyte growth factor, vascular endothelial cell growth factor, and platelet-derived growth factor protein expression. IGF-I cDNA had no effect on transforming growth factor-beta. IGF-I cDNA significantly increased type IV collagen while it had no effect on types I and III collagen. Exogenously administered IGF-I cDNA increased protein concentrations of keratinocyte growth factor, fibroblast growth factor, platelet-derived growth factor, and type IV collagen. We conclude that liposomal IGF-I gene transfer can accelerate wound healing without causing an increase in types I and III collagen expression.

Animals↗