Biomedical subjects

Robert E Barrow

Publications and source records attributed to Robert E Barrow.

26 records · Page 2Linked to original sources

PubMed2003

Recombinant human growth hormone increases thyroid hormone-binding sites in recovering severely burned children.

Thyroxine (T4), Tri-iodothyronine (T3), and total serum protein levels are reduced in severely burned children. T4 and T3 are carried on serum transport proteins via thyroid hormone-binding sites (THBS). Treatment of bums with recombinant human growth hormone (rhGH) increases albumin (Alb) and prealbumin (PreAlb), which bind nearly 30% of circulating T4 and T3. This study investigated the effect of rhGH on THBS sites in burned children. Records of 11 acutely burned children with a total body surface area burned >40% who were randomized to either a daily subcutaneous injection of rhGH at 0.05 mg/kg/day or placebo for 6 months after discharge from hospital were reviewed. Thyroxine uptake percentage (TU%), Total T4 levels (TT4), free thyroxine index, Alb and PreAlb, and height and weight measurements taken at discharge and 6 months later were compared in both groups. In the six children who received rhGH, mean TU% had decreased from 41 +/- 1 to 33 +/- 1% by 6 months postdischarge, (P < 0.001), mean TT4 increased from 5.8 +/- 0.3 to 8.1 +/- 0.8 microg/dL, (P < 0.02), mean Alb increased from 2.0 +/- (0.6) to 3.5 +/- (0.1) g/dL (P < 0.0001), and mean PreAlb increased from 8.7 +/- 0.7 to 16.5 +/- 2.1 mg/dL, (P < 0.006). There were no significant changes in the five children in the placebo (control group), and height and weight did not significantly change in either group. rhGH significantly increases THBS in severely burned children, possibly through increases in serum Alb and PreAlb. The increases in circulating thyroxine observed in this group may be involved in the attenuation of growth arrest.

Blood Glucose↗

PubMed2003

Gene expression patterns in skeletal muscle of thermally injured children treated with oxandrolone.

OBJECTIVE: To analyze gene expression patterns in skeletal muscle from burned children. SUMMARY BACKGROUND DATA: Analysis of gene expression patterns in skeletal muscle from burned children can help provide a fundamental understanding of muscle wasting at the molecular level. This study is the first to use such an approach in burned children receiving anabolic treatment. METHODS: Children who received 0.1 mg/kg oxandrolone twice a day (n = 7) were compared to placebo (n = 7). Net protein balance was determined before and after treatment with oxandrolone. Total RNA, extracted from muscle biopsies obtained from burned children age 3 to 18 years, was purified, reverse transcribed, and biotinylated cRNA hybridized to the human high-density oligonucleotide array (U95Av2). Western blot analysis verified the mRNA changes at their protein level. RESULTS: DNA microarray analysis showed two genes significantly changed in muscle from burned children receiving placebo, while the expression of 21 genes was altered with oxandrolone. Muscle net protein balance increased with oxandrolone treatment compared to placebo. CONCLUSIONS: DNA microarray technology will help identify molecular changes that can serve as targets for new therapies to attenuate muscle wasting in severely burned children and thus improve recovery and early rehabilitation.

Adolescent↗

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

Gene expression analysis in burn wounds of rats.

The events occurring early in the burn wound trigger a sequence of local and systemic responses that influence cell and tissue survival and, consequently, wound healing and recovery. Using high-density oligonucleotide arrays we identified gene expression patterns in skin samples taken from a region of injury in the burn rat model. The associated genomic events include the differential expression of genes involved in cell survival and death, cell growth regulation, cell metabolism, inflammation, and immune response. The functional gene cluster detected and their time appearance matched the time sequence known to occur in burn wound healing.

Animals↗

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↗

PubMedDate not supplied

Dietary fat composition alters pulmonary function in pigs.

OBJECTIVES: We investigated the effect of various dietary fats on pulmonary surfactant composition and lung function changes that occur before and after endotoxin infusion in pigs. METHODS: Eighteen pigs were assigned to three groups (n = 6 per group) to receive a diet of protein (20% of calories), carbohydrate (20% of calories), and fat (40% of calories). In one group the fat content consisted entirely of palmitic acid. In the second group, fat came from Intralipid, which provided predominantly linoleic acid. The third group was fed fish oil. Pigs were maintained on these diets for 21 d before the experiment. Cardiovascular and pulmonary functions were determined on day 22. Pigs then were infused with endotoxin (80 mg. kg(-1). min(-1)) until the pulmonary arterial pressure reached a pressure similar to that found in trauma victims (45 to 50 mmHg). Cardiovascular and pulmonary function tests were then repeated, the animals killed, and the lungs removed for study. RESULTS: Compliance was reduced in the linoleate and fish-oil groups compared with the palmitate group before and after endotoxin. Compliance changes in pigs fed the linoleate and fish-oil diets were consistent with significant increases in lung wet:dry weight ratios, increased CO(2) retention, histologic evidence of vascular congestion, intra-alveolar edema, and alveolar septa thickening. Changes in surfactant phosphatidylcholine composition between groups were consistent with the notion that increased unsaturated fatty acids could affect surfactant function. CONCLUSIONS: We concluded that the common practice of providing calories in the form of polyunsaturated fatty acids to critically ill patients carries the risk of being detrimental to lung function.

Animals↗

PubMedDate not supplied

Matrix metalloproteinases and their tissue inhibitors in severely burned children.

Severe burns cause not only skin injury but several marked systemic derangements. During wound healing, matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases play an important role in tissue regeneration and remodeling processes. Therefore, in the present study, we determined the serum levels of MMPs and tissue inhibitor of metalloproteinase-1 in burn patients over time. Serum samples from 12 severely burned children (mean age 7.9 +/- 2.5 years) with >40% total body surface area burns were obtained within 0.5 hours, 3, 7, and 21 days after injury. Pro-MMP-1, MMP-3, MMP-9, and tissue inhibitor of metalloproteinase-1 serum levels were assayed by enzyme-linked immunoassay and compared to normal healthy volunteers. Two-way analysis of variance and Bonferroni's test were used for statistical analysis. Pro-MMP-1 levels in the serum were significantly elevated by the seventh day after burn. MMP-3 and MMP-9 levels showed significant increases by day 3 and 21 compared to normals, respectively. Tissue inhibitor of metalloproteinase-1 levels did not change with time after burn but were significantly higher by 3 days after burn compared to normal serum. In conclusion, changes in MMPs and tissue inhibitor of metalloproteinase-1 occur in burn patients and those changes may be a mechanism beneficial to wound healing.

Analysis of Variance↗

PubMedDate not supplied

Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children.

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.

Burns↗