Search PubMed⌕ Search

Biomedical subjects

R E Barrow

Publications and source records attributed to R E Barrow.

At least 55 records · Page 3Linked to original sources
PubMed1997

Growth hormone improves immune function and survival in burned mice infected with herpes simplex virus type 1.

Recombinant human growth hormone (rhGH) is often used clinically for the treatment of burned patients to promote wound healing and to improve protein metabolism. Recently, the immunomodulatory activity of GH has been described, but it remains unclear whether immune abnormalities associated with burn are improved by rhGH administration. To determine the immunoregulatory activities of rhGH in thermal injury, the survival of burned mice infected with herpes simplex virus type 1 (HSV-1), along with interferon-gamma (IFN-gamma) production by splenic mononuclear cells (SMNCs), and generation of cytostatic macrophages in burned mice were examined after exogenous administration of rhGH. Data showed that the mortality after HSV-1 infection was improved in burned mice treated with a 4-mg/kg dose of rhGH every other day for five doses. Also, the decreased IFN-gamma response of SMNCs from burned mice improved with rhGH therapy. Further, cytostatic macrophages were generated in burned mice treated with rhGH, whereas these macrophages were not demonstrated in burned mice treated with saline. These results indicate that rhGH can improve immune function in burned mice, specifically improving survival in HSV-1 infection, boltering IFN-gamma production by SMNCs, and increasing production of cytostatic macrophages.

Animals↗
PubMed1997

Mortality determinants in massive pediatric burns. An analysis of 103 children with > or = 80% TBSA burns (> or = 70% full-thickness).

OBJECTIVE: Survivors and nonsurvivors among 103 consecutive pediatric patients with massive burns were compared in an effort to define the predictors of mortality in massively burned children. SUMMARY BACKGROUND DATA: Predictors of mortality in burns that are used commonly are age, burn size, and inhalation injury. In the past, burns over 80% of the body surface area that are mostly full-thickness often were considered fatal, especially in children and in the elderly. In the past 15 years, advances in burn treatment have increased rates of survival in those patients treated at specialized burn centers. The purpose of this study was to document the extent of improvement and to define the current predictors of mortality to further focus burn care. METHODS: Beginning in 1982, 103 children ages 6 months to 17 years with burns covering at least 80% of the body surface (70% full-thickness), were treated in the authors' institution by early excision and grafting and have been observed to determine outcome. The authors divided collected independent variables from the time of injury into temporally related groups and analyzed the data sequentially and cumulatively through univariate statistics and through pooled, cross-sectional multivariate logistic regression to determine which variables predict the probability of mortality. RESULTS: The mortality rate for this series of massively burned children was 33%. Lower age, larger burn size, presence of inhalation injury, delayed intravenous access, lower admission hematocrit, lower base deficit on admission, higher serum osmolarity at arrival to the authors' hospital, sepsis, inotropic support requirement, platelet count < 20,000, and ventilator dependency during the hospital course significantly predict increased mortality. CONCLUSIONS: The authors conclude that mortality has decreased in massively burned children to the extent that nearly all patients should be considered as candidates for survival, regardless of age, burn size, presence of inhalation injury, delay in resuscitation, or laboratory values on initial presentation. During the course of hospitalization, the development of sepsis and multiorgan failure is a harbinger of poor outcome, but the authors have encountered futile cases only rarely. The authors found that those patients who are most apt to die are the very young, those with limited donor sites, those who have inhalation injury, those with delays in resuscitation, and those with burn-associated sepsis or multiorgan failure.

Adolescent↗
PubMed1996

Growth hormone and IGF-I therapy in the hypercatabolic patient.

The use of exogenous GH to increase its circulating concentration, may benefit critically ill patients by increasing their nitrogen retention and promoting the wound healing process. GH also changes protein production in wounds, causes higher levels of insulin and changes substrate utilization. Its effects are anabolic, diabetogenic and lipolytic, acting through both direct and indirect mechanisms. The effects on carbohydrate and fat metabolism are directly mediated through specific GH receptors, while its effect on protein is mediated through IGF-I. Its effects on IGF-I production and the induction of IGF binding proteins are currently being studied in an effort to better understand the mechanism of GH actions during stress.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Beta-blockade lowers peripheral lipolysis in burn patients receiving growth hormone. Rate of hepatic very low density lipoprotein triglyceride secretion remains unchanged.

OBJECTIVE: The purpose of this study was to determine the effect of propranolol on peripheral lipolysis in massively burned children during treatment with recombinant human growth hormone (rhGH), and to ascertain whether decreased free fatty acid availability for re-esterification would alter the hepatic rate of secretion of triglycerides (TGs) bound to very low density lipoproteins (VLDLs). BACKGROUND: Fatty liver occurs in severely burned patients, often resulting in a twofold increase in liver size. This could be the result of an imbalance between increased provision of free fatty acids from peripheral lipolysis, coupled with no increase in fat oxidation, and insufficient rate of secretion of TGs from the liver. METHODS: In a cross-over study, six burned children were treated with either rhGH or rhGH plus propranolol. On the sixth day of treatment, isotopic tracer infusions were conducted to determine the rate of release of free fatty acid (Ra FFA) from peripheral tissue and the rate of secretion of VLDL-bound TGs by the liver. RESULTS: Exogenous rhGH increased Ra FFA in children with large third-degree burns. Propranolol decreased Ra FFA, but the rate of secretion of fatty acids in the form of VLDL-TG from the liver was maintained. Plasma FFA, as opposed to fatty acids newly synthesized in the liver, were the primary precursors for hepatic triglyceride synthesis. CONCLUSIONS: The administration of propranolol to burned children receiving rhGH is safe, has salutary cardiovascular effects, decreases the release of FFA from adipose tissue and increases the efficiency of the liver in secreting fatty acids as VLDL TGs.

Adolescent↗
PubMed1996

Combined insulin-like growth factor-1 and growth hormone improves weight loss and wound healing in burned rats.

UNLABELLED: The anabolic effects of growth hormone (GH) in burned patients appear to act both directly and through insulin-like growth factor-1 (IGF-1). We, therefore, hypothesize that exogenous GH plus IGF-1 will attenuate increases in metabolism and lean muscle wasting while promoting wound healing. MATERIALS AND METHODS: Rats, each weighing 440-470 g, were given a 35% total body surface area, full-thickness scald burn and divided into four groups to receive placebo (burned controls), bovine GH (2.5 mg/kg/day), IGF-1 (2.0 mg/kg/day), or bovine GH plus rhIGF-1 (2.5 + 2.0 mg/kg/day), respectively, for 8 weeks. RESULTS: Total body weight gain after 8 weeks averaged 110 g for GH plus IGF-1 compared with gains of 49 and 11 g for GH or IGF-1 alone, respectively. Burned controls lost 24 g. Metabolic rates were significantly reduced in all groups receiving growth hormones. Gastrocnemius muscle dry weight was significantly increased in those receiving GH plus IGF-1 compared with GH and IGF-1 alone or burned controls (p < .01). CONCLUSIONS: Data show that GH plus IGF-1 synergistically increased lean muscle weight, total body weight, and was more effective in re-epithelialization of the burn wound than either GH or IGF-1 alone.

Animals↗
PubMed1996

Growth hormone treatment for burned children.

Several growth hormones show promise in the treatment of burn injuries, particularly for paediatric patients. Animal studies and clinical trials indicate that growth hormones help modulate the devastating effects of the hypermetabolic response to burn injury and improve wound healing. Recombinant human growth hormone (rhGH) has been shown to reduce loss of body weight, stimulate protein synthesis, increase epithelial cell proliferation, and accelerate wound healing. Accelerated wound closure reduces the risk of infection, shortens hospital stay, and lowers overall medical costs. Current investigations are in progress to determine the effects of rhGH on anabolic growth arrests experienced by paediatric burn survivors.

Burns↗
PubMed1995

Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns.

BACKGROUND: Human growth hormone is an anabolic agent that attenuates injury-induced catabolism and stimulates protein synthesis. Recombinant human growth hormone (rhGH) administered therapeutically to patients with massive burns has been shown to increase the rate of skin graft donor site healing. It has been postulated that growth hormone affects wound healing and tissue repair by stimulating the production of insulin-like growth factor-1 (IGF-1) by the liver to increase circulating IGF-1 concentrations. The mechanism by which it improves wound healing, however, remains in question. The authors hypothesize that rhGH up-regulates IGF-1 receptors and IGF-1 levels both systemically and locally in the wound site to stimulate cell mitosis and increase synthesis of laminin, collagen types IV and VII, and cytokeratin. This hypothesis was tested in nine patients with burns covering > 40% of total body surface area. OBJECTIVE: The authors assessed the efficacy of rhGH in promoting several major building materials in the donor site of patients with massive burns. METHODS: Ten massively burned patients with full-thickness burns covering more than 40% of total body surface area were participants in a placebo-controlled prospective study to determine the efficacy of 0.2 mg/kg/day rhGH on donor site wound healing and to identify some of the major components involved in wound healing and its integrity. RESULTS: Donor sites in burn patients receiving rhGH showed an increased coverage by the basal lamina of 26% for placebo to 68% coverage of the dermal-epidermal junction. Insulin-like growth factor-1 receptors and laminin, types IV and VII collagen, and cytokeratin-14 all increased significantly. Healing times of the donor sites were significantly decreased compared with patients receiving placebo. CONCLUSION: Results indicate that growth hormone or its secondary mediators may directly stimulate the cells of the epidermis and dermis during wound healing to produce the structural proteins and other components needed to rebuild the junctional structures.

Adolescent↗
PubMed1994

Lipolysis in burned patients is stimulated by the beta 2-receptor for catecholamines.

OBJECTIVE: To determine if the cardiovascular effects of excessive catecholamines could be selectively blocked in severely burned patients without adversely affecting protein or fat kinetics. DESIGN: Prospective cohort study. SETTING: A large tertiary care referral center in Galveston, Tex. PATIENTS: Sixteen patients with greater than 40% body surface area burns. INTERVENTIONS: Patients were randomly selected to receive propranolol hydrochloride, a nonselective beta 1- and beta 2-blocker, or metoprolol tartrate, a selective beta 1-blocker. MAIN OUTCOME MEASURES: Heart rate; rate-pressure product; rate of appearance of urea, glucose, and leucine; and leucine oxidation were measured before and after selective or nonselective beta-adrenergic blockade. RESULTS: Propranolol and metoprolol caused a significant decrease in heart rate, from a mean (+/- SD) of 143 +/- 15 to 115 +/- 11 and from 147 +/- 17 to 120 +/- 9 beats per minute, respectively, during the 5-day study period. Neither the rate of appearance of urea nor the rate of urea production were significantly altered by propranolol or metoprolol therapy. Only propranolol produced a significant decrease (P < .05) in the rate of appearance of glycerol, from a mean (+/- SD) of 5.54 +/- 0.62 to 3.07 +/- 0.7 mumol/kg per minute. The rate of appearance of leucine, used as an index of total body protein catabolism, was not significantly altered by either beta-blocker. CONCLUSIONS: Selective beta 1-adrenergic blockade did not reduce lipolysis; however, a beta 1- and beta 2-adrenergic blockade significantly reduced lipolysis. Thus, the increased lipolysis, characteristic of severely burned patients, is caused by stimulation of the beta 2-adrenergic receptors for catecholamines.

Adolescent↗
PubMed1994

Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns.

OBJECTIVE: Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated. SUMMARY BACKGROUND DATA: Growth hormone has been shown to reduce wound healing times in burned pediatric patients. Through genetic engineering, several different forms have been synthesized; however, not all are marketed currently. Two forms of growth hormone were used in these studies, Protropin (Genentech, Inc., San Francisco, CA), a commercially available product that possesses a N-terminal methionine residue not found in the second form Nutropin (Genentech, Inc., San Francisco, CA), which, as yet, is not commercially available. Through the use of recombinant human growth hormone, rapid wound healing may reduce the hypermetabolic period, the risk of infection, and accelerate the healing of donor sites used for grafting onto burned areas. The two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children. METHODS: Forty-six children, with a > 40% total body surface area and > 20% total body surface area full-thickness burn were entered in a double-blind, randomized study to receive rhGH within 8 days of injury. Twenty received (0.2 mg/kg/day) Nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision. Eighteen patients who failed the entry criteria for receiving Nutropin received Protropin therapeutically (0.2 mg/kg/day). Donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with Scarlet Red impregnated fine mesh gauze (Sherwood Medical, St. Louis, MO). The initial donor site healing time, in days, was reached when the gauze could be removed without any trauma to the healed site. RESULTS: Donor sites in patients receiving Nutropin (n = 20) or Protropin (n = 18) healed at 6.8 +/- 1.5 and 6.0 +/- 1.5 (mean +/- SD) days, respectively, whereas those receiving placebo (n = 26) had a first donor site healing time of 8.5 +/- 2.3 days. Both groups receiving rhGH showed a significant reduction in donor site healing time compared with placebo at p < 0.01. When subgroups were compared, no difference in healing times could be shown with regards to age or time of admission after injury. CONCLUSION: Our results indicate that both forms of rhGH are effective in reducing donor site healing time compared with placebo and suggest that accelerating wound healing is of clinical benefit because the patients' own skin becomes rapidly available for harvest and autografting. With this increase in the rate of wound healing, the total length of hospital stay can be reduced by more than 25%.

Adolescent↗
PubMed1994

Pulmonary inflammatory cell response to sustained endotoxin administration.

We have developed a model of human sepsis in sheep. Twenty-four hours after continuous infusion of Escherichia coli endotoxin (lipopolysaccharide) (10 ng.kg-1.min-1) was begun, pulmonary transvascular fluid flux was almost five times the baseline values, cardiac output was nearly doubled, and mean arterial pressure was reduced by approximately 20 mmHg. At this time, the animals were killed and their lungs were fixed by endotracheal installation of 2.5% glutaraldehyde at 25 cmH2O pressure. Morphometry was performed by point counting, and data were expressed as relative volume density. Pulmonary edema and congestion were observed in sheep receiving lipopolysaccharide, whereas sham controls appeared normal. There was an increase in interstitial volume density. There was a significant increase (P < 0.01) in volume density of the pulmonary intravasculature (180%), interstitial macrophages (270%), and mast cells (240%). The volume densities of intravascular and interstitial polymorphonuclear neutrophils also showed a small insignificant increase.

Animals↗
PubMed1994

Efficacy of cefazolin in promoting ovine tracheal epithelial repair.

Inhalation of toxic materials has been shown injurious to the upper airways. Because secondary infection can slow the repair process, we undertook this study to determine the efficacy of antibiotic therapy in promoting the healing process of acute tracheal wounds. In 18 anesthetized sheep, a portion of the cervical trachea was exposed to smoke from smoldering cotton cooled to 38 degrees C. Nine received the broad-spectrum antibiotic, cefazolin, while none received saline placebo. At 13 days after injury, nonciliated and ciliated cell counts were 75% and 33% respectively of noninjured trachea receiving placebo, while in those receiving cefazolin, nonciliated and ciliated cell counts increased to 93% and 114% of paired noninjured trachea, respectively. We suggest that cefazolin therapy allows cell proliferation and differentiation to proceed more rapidly than observed with placebo therapy and thus may be a helpful augmentor to the healing of an acute airway injury.

Animals↗
PubMed1993

Growth factors accelerate epithelial repair in sheep trachea.

Toxic gases and fumes have been shown to be injurious to the upper airways. Repair of this injury involves proliferation and migration of surviving nonciliated cells, followed by differentiation to a normal phenotype. Because recent results suggested that growth factors could improve the outcome of an airway injury, we undertook this study to determine the efficacy of these materials as an initial treatment to accelerate the healing process. In 24 anesthetized sheep, a portion of the trachea was exposed to smoke from smouldering cotton cooled to 37 degrees C. Twelve received aerosolized epidermal growth factor plus platelet derived growth factor, while twelve received placebo. At 10 days after injury, nonciliated and ciliated cells were totally absent in the injured trachea receiving the placebo. In animals receiving growth factors, nonciliated and ciliated cells, however, were present (56% and 31% of uninjured trachea, respectively). At 13 days after injury, nonciliated and ciliated cell counts in those receiving placebo were 67% and 33% of uninjured, respectively. In sheep receiving growth factors, tracheal nonciliated and ciliated cell counts had increased to 105% and 64% of uninjured trachea, respectively. We conclude that growth factors therapy after airway injury stimulates cell proliferation and differentiation, and this therapeutic intervention to accelerate the repair process in acute airway injury is an approach applicable to humans.

Animals↗
PubMed1993

Influence of detergent aerosol on lung microvascular permeability.

Noncardiogenic edema fluid often contains high levels of plasma proteins, which may inhibit the function of the lung surfactant complex and thus decrease interstitial hydrostatic pressures. We questioned whether, in the awake and standing animal, displacement of the alveolar surface lining would alter the permeability of the thin and sparsely supported pulmonary capillaries. Sheep prepared with lung lymph fistulae were given an aerosolized detergent (Det) to displace the lung surfactant complex. After the sheep were given Det, protein flux was significantly increased (P < 0.05). To validate the suggested permeability increase, pulmonary vein occluders were surgically implanted and experiments repeated with pulmonary arterial pressures elevated 10 mmHg above baseline. After 2 h of elevated pulmonary arterial pressure, lung lymph increased fivefold. At this time, lymph-to-plasma total protein concentration ratios for air and saline-plus-ethanol vehicle were significantly lower (P < 0.01) than baseline ratios (0.26 +/- 0.06 and 0.34 +/- 0.07, respectively). No significant difference could be shown in lymph-to-plasma ratios after the sheep were given Det. We conclude that disruption of the alveolar lining can cause a detectable increase in protein flux due, in part, to an increase in microvascular permeability.

Aerosols↗
PubMed1992

Cellular sequence of tracheal repair in sheep after smoke inhalation injury.

The cellular repair process of injured tracheal epithelium is described for sheep after exposure to toxic smoke containing high concentrations of acrolein. Fourteen fasted 3-4-year-old ewes had a portion of their cervical trachea exposed to cotton smoke for 20 min and then were sacrificed at various time intervals ranging from 1 to 22 days after exposure. Within 1 day of injury, columnar epithelium sloughed intact from the trachea with a concomitant reduction of nearly 35% in the basal cell population. At 2 days of recovery, the cellularity of the epithelium had increased and mitotic figures were observed in some tracheal epithelial and gland cells. By 8 days, undifferentiated hyperplastic cells increased to 30/100 microns, differentiated nonciliated columnar cells first appeared, and the basal cell population returned to a normal count of 13 cells/100 microns. Thirteen days after exposure, the undifferentiated hyperplastic cell population had declined to 7 cells/100 microns, nonciliated columnar cells were at control values, and some ciliated cells were identified. At 18 and 22 days, epithelium was normal in appearance and the count was 13 cells/100 microns. Data suggest that because the columnar epithelium sloughs intact with the cilia remaining active, toxic smoke may affect their attachment to the basal lamina. Furthermore, the regeneration process involves differentiation of hyperplastic cells in which they elongate down to the basal lamina, thus re-establishing the integrity of tall epithelium in the sheep trachea.

Animals↗
PubMed1992

Morphologic changes in basal cells during repair of tracheal epithelium.

Basal cells are differentiated with respect to junctional adhesion mechanisms and play a role in attachment of columnar epithelium to the basal lamina. Although much is known about nonciliated and ciliated cell differentiation during the repair process after injury, little is known about the basal cell. We studied the morphology of basal cells and quantitated junctional adhesion structures during repair of tracheal epithelium exposed to toxic cotton smoke. Ten adult ewes were given a smoke injury to a portion of the upper cervical trachea and were killed at 4, 6, 8, 10, and 18 days after injury for morphometric studies. At 4 days, there was a stratified reparative epithelium over the basal lamina, which was two to four cells in depth. The basal cells were identified by their hemidesmosome (HD) attachment to the basal lamina. Basal cells were about 69% larger than controls and flattened rather than columnar. The amount of HD attachment was 192% greater than controls. In contrast, volume density of cytokeratin filaments had decreased about 47%. Basal cells had returned to normal numbers and size and a columnar shape by day 18. The amount of desmosome (D) and HD attachment and volume density of cytokeratins had also reached control levels by day 18. These data indicate that morphology of basal cells changes during the initial stages of reparative regeneration but returns to normal by 18 days. Morphologic changes appear to reflect changes in size of the cell associated with cell division rather than differentiation of recently divided basal cells.

Animals↗
PubMed1992

Effect of recombinant human growth hormone on catabolic hormones and free fatty acids following thermal injury.

Severe burn injury elicits the release of catabolic hormones that contribute to negative nitrogen balance, protein wasting, and impaired wound healing. Previous studies have shown that burn patients receiving recombinant human growth hormone (rhGH) therapy have an increase in the rate of skin donor site healing and a shorter hospital stay. The mechanism by which rhGH exerts its effects, however, is not clearly understood. This study examines the effects of rhGH on circulating levels of catabolic hormones and nonesterified fatty acids in pediatric burn patients. Patients with greater than 40% total body surface area burn were randomly assigned to receive placebo (n = 8) or 0.2 mg/kg/day rhGH (n = 6) throughout their hospitalization. All patients had early morning blood samples assessed for catecholamines (CAT), cortisol, insulin, glucagon, and free fatty acid (FFA) levels during a period of hypermetabolism. No differences could be demonstrated in age, burn size, postburn day of evaluation, resting energy expenditure per kilogram, respiratory rate, heart rate, respiratory quotient, serum cortisol, and serum glucose between placebo- and rhGH-treated patients. The rhGH-treated group did show a significant elevation (p less than 0.05) in insulin-like growth factor-1 (55.9 +/- 14.5 vs. 168 +/- 23.7 mU/mL), total catecholamines (1,817 +/- 177 vs. 1,117 +/- 137 pg/mL), norepinephrine (1,257 +/- 121 vs. 867 +/- 113 pg/mL), epinephrine (385 +/- 175 vs. 147 +/- 36 pg/mL), insulin (32.8 +/- 3.3 vs. 25.0 +/- 3.0 mU/mL), glucagon (215 +/- 18 vs. 158 +/- 22 pg/mL), and free fatty acids (0.74 +/- 0.01 vs. 0.59 +/- 0.04 mEq/L) compared with the placebo group (data expressed as mean +/- SE).(ABSTRACT TRUNCATED AT 250 WORDS)

Burns↗