Search PubMedSearch

Biomedical subjects

R E Barrow

Publications and source records attributed to R E Barrow.

At least 19 recordsLinked to original sources

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

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

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

Propranolol diminishes extremity blood flow in burned patients.

Beta adrenergic blockade diminishes the catecholamine-mediated elevations in heart rate and myocardial contractility that characterize postburn hypermetabolism. To examine how these alterations in cardiac performance affect peripheral perfusion, indirect calorimetry and leg blood flow were measured before and then after a 2-hour intravenous propranolol infusion. Five severely burned patients (55% + 7% total burn surface area), given propranolol at 8 micrograms/kg/minute, had a significant reduction in cardiac index and heart rate with an increased leg vascular resistance resulting in a decrease in extremity perfusion. Four healthy volunteers were given propranolol at 5 micrograms/kg/minute, resulting in a comparable decrease in heart rate, yet there was no change in leg vascular resistance or extremity perfusion. In both patient groups, propranolol decreased the plasma lactate concentration. This suggests that in hypermetabolic patients, beta adrenergic blockade reduces peripheral perfusion and that peripheral perfusion is not a principal determinate of plasma lactate levels. Rather adrenergic blockade appears to decrease lactate concentration as a consequence of the inhibition of lipolysis.

Adult

Tracheal venous blood and lymph collection: a model to study airway injury in sheep.

Airway injury is a frequent result of the inhalation or aspiration of toxic material. Although upper airway damage can be identified endoscopically, pathophysiological changes are difficult to evaluate. This paper describes an animal model in which changes in tracheal blood and lymph flow rates, wet-to-dry weight ratios, and lymph-to-plasma protein ratios can be evaluated after injury. In this model, 12 cm of the cervical trachea were isolated using a double-cuffed endotracheal tube and injured with cotton smoke at near room temperature. Injury to the trachea was evaluated in twenty-five anesthetized sheep 4 (n = 3), 8 (n = 3), 24 (n = 3), 48 (n = 3), 96 (n = 3), and 192 (n = 2) h after smoke exposure and compared with sham control animals (n = 8). A significant increase in tracheal venous blood flow from 1.3 +/- 0.4 (SD) ml.min-1.cm-1 for the noninjured trachea to 2.8 +/- 1.2 was noted 24 h after injury (P less than 0.01). Lymph flow significantly increased from 1.3 +/- 0.4 microliters.min-1.cm-1 for the noninjured trachea to 9.8 +/- 3.3 24 h after injury while wet-to-dry weight ratios were elevated from 3.0 +/- 0.2 for noninjured trachea to 4.6 +/- 0.9 from 4 to 24 h after injury (P less than 0.01) and decreased to 3.7 +/- 0.5 by 96 h. Cast material consisting of airway exudate, cellular debris, and intact ciliated epithelial cells was both expectorated and found in the trachea when the animals were killed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Chemical structure of phospholipids in the lungs and airways of sheep.

Experiments on phospholipids from the alveolar lining, bronchi and trachea were conducted to support the concept that different lipid complexes are synthesized and released at different sites in the pulmonary system. Tracheal, bronchial and bronchioalveolar lavages were obtained from healthy adult Merino breed ewes following euthanasia and a structural analysis of the phospholipid fraction made by fast atom bombardment mass spectrometry. The major components in tracheal lavage were: 72% phosphatidylcholines (PC), 8% phosphatidylethanolamines (PE) and 11% phosphatidylglycerols (PG) compared to 78% PC, 13% PE and 3% PG in bronchioalveolar lavage. The fatty acid profile of tracheal lavage showed that 73% of the PG and 3% of the PC contained an arachidonic acid side chain. These species were not found in bronchioalveolar lavage. The nearly four-fold increase in PG, and the different molecular species identified in tracheal compared to bronchioalveolar lavage, suggest local synthesis and release of phospholipids by tracheal epithelial cells. The distribution of these phospholipids may have functional properties desirable for normal mucociliary function and are consistent with published measurements from cultured tracheal epithelia cells.

Animals

Early burn wound excision significantly reduces blood loss.

The hypothesis that near-total early excision of large burns in children can be performed safely with a reduction in blood loss was tested. Of 1662 acutely burned patients admitted to this institution between 1982 and 1989, 594 underwent near-total excision of cutaneous flame or scald burn injuries in a single procedure. Operations took less than 3 hours and there were no operative deaths. Blood losses in burns of more than 30% total body surface area (TBSA) were significantly less at 0.40 +/- 0.06 mL/cm2 and 0.49 +/- 0.49 mL/cm2 excised when surgery was performed within the first 24 hours or after the 16th day after burn, respectively, when compared to 0.75 +/- 0.02 mL/cm2 for those excised between 2 and 16 days after burn (p less than 0.05). Blood loss for burns of less than 30% TBSA was of 1.19 +/- 0.13 mL/cm2. Early excision did not increase mortality rate when compared to later excision times. We suggest that near-total excision of large burns within the first 24 hours reduces blood requirements and morbidity without adversely altering hemodynamic stability or increasing mortality risks.

Blood Transfusion

Effects of recombinant human growth hormone on donor-site healing in severely burned children.

The beneficial effects of growth hormone on wound healing in severely burned children were studied. Forty patients who were 2 to 18 years old, with 40% or more total body surface area (TBSA) and 20% or more TBSA full-thickness flame or scald burns, were randomized in a double-blind study to receive placebo or 0.1 mg/kg/day recombinant human growth hormone (rHGH) until the first donor site healed or to receive 0.2 mg/kg/day rHGH or placebo from admission throughout hospitalization. Patients receiving 0.2 mg/kg/day rHGH demonstrated significantly higher serum IGF-1 levels at 4.8 +/- 1.7 U/mL compared to placebos at 1.6 +/- 0.4 U/mL (p less than 0.05) and a significant decrease in donor-site healing times compared to placebo (p less than 0.05). Length of hospital stay (LOS/%TBSA) was decreased from 0.80 +/- 0.10 days/%TBSA burned in the placebo group to 0.54 +/- 0.04 days/%TBSA burned in the 0.2 mg/kg/day treatment group (p less than 0.05). This translates, for the average 60% TBSA burned patient, to a decrease in LOS from 46 to 32 days.

Adolescent

Selective permeability changes in the lungs and airways of sheep after toxic smoke inhalation.

The effect of toxic smoke inhalation on selective microvascular sieving of macro-molecules and lymph protein flux was assessed in adult sheep to determine whether the time course of microvascular dysfunction differs between the lung and trachea. Protein flux across the lung increased sixfold 48 h after inhalation of the products of incomplete cotton combustion, whereas tracheal protein flux increased fivefold 8 h after exposure and returned to near base line 48 h after exposure. The lung and trachea selectively retained some sieving to three different protein macromolecules with molecular radii of 36, 54, and 123 A. In the lungs the sieving selectivity for these macromolecules was least 48 h after injury, and in the trachea molecular selectivity was least 8 h after injury. These data suggest that the time course of microvascular injury differs for the trachea and the lung; microvascular changes are detected earlier in the trachea than in the lung. The inhalation injury described thus permits the characterization of the time course of airway and lung microvascular changes.

Animals

Incidence of mortality in boys and girls after severe thermal burns.

One hundred and eighty-five children with burns, 118 boys and 67 girls, all of whom had thermal burns covering more than 30 per cent of the body surface area without complications from inhalation injury, were studied to determine whether boys or girls better survive massive skin burns and if a high mortality group within these populations could be identified. A significantly higher mortality rate (15 per cent) was noted for boys when compared with girls (3 per cent), with 44 per cent of the deaths in boys identified in the greater than 95th percentile body weight-for-age distribution.

Adolescent

Improved myocardial oxygen utilization following propranolol infusion in adolescents with postburn hypermetabolism.

The purpose of this study was to determine if propranolol (0.5 mg/kg and 1 mg/kg), administered intravenously (IV) at the height of the postburn hypermetabolic response, would decrease myocardial oxygen requirements, without adversely affecting overall oxygen delivery or total body oxygen consumption. To test this hypothesis, six nonseptic patients age 17 +/- 3 years with burns over 82% +/- 11% total body surface area were given propranolol with continuous hemodynamic monitoring. Propranolol was administered to these patients 20 +/- 15 days postburn. Two clinically derived indices of myocardial oxygen consumption, pressure-work index (PWI) and rate-pressure product (RPP), were used to estimate the energy expenditure of the working heart. Both PWI and RPP were significantly decreased from baseline after 0.5 mg/kg propranolol, 31% for PWI (P less than .001) and 30% for RPP (P less than .01). Similarly, a decrease from baseline was seen after 1.0 mg/kg propranolol, 32% for PWI (P less than .001) and 35% for RPP (P less than .01). Cardiac index (L/min/m2) demonstrated no significant change [7.4 +/- 1.1 (prepropranolol), 6.5 +/- 1.3 (after 0.5 mg/kg propranolol), and 6.8 +/- 1.0 (after 1.0 mg/kg propranolol)] and exceeded the upper limits of normal (hyperdynamic state) throughout the study. Oxygen delivery index (962 +/- 209 mL/min/m2) and oxygen consumption indices [(254 +/- 78 mL/min/m2 by Fick method and 236 +/- 78 mL/min/m2 by inspired and expired gases)] were elevated at baseline and unaffected by propranolol. The decrease in PWI and RPP was achieved mainly by propranolol's effect to lower both heart rate and BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A comparison of conservative versus early excision. Therapies in severely burned patients.

Early excision and grafting of small burn wounds is a generally accepted treatment. Early excision of burn injuries greater than 30% total body surface area (TBSA) in adults, however, has not been universally accepted. In this study, 85 patients whose ages ranged from 17 to 55 years with greater than 30% total body surface area (TBSA) burns were randomly assigned to either early excision or topical antimicrobial therapy and skin grafting after spontaneous eschar separation. Mortality from burns without inhalation injury was significantly decreased by early excision from 45% to 9% in patients who were 17 to 30 years of age (p less than 0.025). No differences in mortality could be demonstrated between therapies in adult patients older than 30 years of age or with a concomitant inhalation injury. Children (n = 259) with similar large burns treated by early excision showed a significant increase in mortality with increasing burn size and with concomitant inhalation injury (p less than 0.05). The mean length of hospital stay of survivors was less than one day per per cent of TBSA burn in both children and adults.

Adolescent

Morphological studies on the venous drainage of the trachea in the neck of sheep.

Systemic venous drainage of the cervical portion of the trachea from the cricoid cartilage to the sternal notch was observed in 50 adult sheep. In all animals, the first five to six tracheal rings starting at the cricoid cartilage were drained by the thyroid veins (v. thyroideae) bilaterally to the external jugular veins (v. jugularis externa). A venous complex draining the remaining cervical portion of the trachea was observed only on the left side of the trachea. This complex drained to the cranial vena cava (vena cava cranialis). India ink or Evans blue dye were infused into small vessels draining this area for verification. Variations in this venous complex were classified into three types based upon length of trachea drained. Type I was found in 26%, type II found in 58%, and type III found in 16% of the sheep studied and drained 23 +/- 5%, 58 +/- 11% and 78 +/- 10% of the cervical portion of the trachea, respectively. Blood flow from this area of the trachea was 85 +/- 28 mL/min/100 g wet issue. This study identified and classified the venous drainage of the cervical portion of the trachea in sheep.

Animals

Inhalation injury in burned patients: effects and treatment.

Pulmonary pathology in major thermal injury is found in 30-80 per cent of burn fatalities. The incidence and mortality from inhalation injury increases both with age and increasing burn size. Toxic smoke inhalation injury, characterized by increased lung microvascular permeability, is attenuated by increasing cardiac output to normal levels, indicating that fluid restriction after inhalation injury may lead to excessive lung fluid formation and hypoxia. Fluid administration of approximately 2 ml/kg/% area burned above the calculated resuscitation volume is required following an inhalation injury to provide adequate support for the systemic circulation and maintain cardiac output at normal levels. This additional volume does not contribute to the development of pulmonary oedema, but may decrease its formation by increasing shear forces thus reducing polymorphonuclear leucocyte deposition in the pulmonary microcirculation. Nasotracheal intubation is preferred when airway integrity is compromised by inhalation injury. The advantages are non-operative placement, ease of discontinuation, minimal bacterial contamination and leaving neck burns undisturbed. The administration of the appropriate antibiotics for documented infection is recommended, while steroids have been shown to be of no benefit.

Adolescent

Effect of propranolol administration on hemodynamic and metabolic responses of burned pediatric patients.

Hypermetabolism, increased heart rate, and lipolysis are responses to high catecholamine levels associated with burn injury. This study tests the hypothesis that adrenergic beta blockade in burns could reduce myocardial work, lipolysis, and negative nitrogen balance without adversely affecting cardiac or metabolic function. Eighteen patients with burns of 70 +/- 3% total burn surface area (TBSA) (Mean +/- SEM), were studied after a 5-day infusion of 2 mg/Kg of intravenous (I.V.) propranolol infusion every 24 hours without their cardiac output or resting energy expenditure being adversely reduced. Heart rate, left ventricular work, and rate pressure product were significantly reduced by 20, 22, and 36%, respectively (P less than 0.05). Plasma glucose, free fatty acids, triglycerides, and insulin levels remained unchanged. The rate of urea production, however, was significantly increased by 54 +/- 12% in fasted patients, and to a much lesser 12 +/- 2% in fed patients. The marked decrease in myocardial work afforded by propranolol administration may be of clinical benefit in the treatment of large burns. Variations in drug dosage and feeding regimens will, however, need to be perfected to limit catabolic effects.

Adolescent