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Biomedical subjects

C R Baxter

Publications and source records attributed to C R Baxter.

At least 37 records · Page 2Linked to original sources

Hydraulic permeability and activation energy of human keratinocytes at subzero temperatures.

Studies on isolated human keratinocytes provide a model for design of optimal freeze-thaw protocols for skin cryopreservation and banking. Nucleated keratinocytes from the basal layer of split thickness human cadaveric skin were separated by a combined trypsin and DNAse digestion and suspended in Dulbecco's minimal essential medium with fetal calf serum. A small volume of suspension was frozen on a microprocessor controlled cryostage. Extracellular ice was nucleated at predetermined subzero temperatures, and the temperature was held constant for the duration of the experiment. The osmotic response of the cells to the formation of extracellular ice was recorded on 35-mm photographic film. Selected serial frames were digitized for automated computer evaluation of metric parameters of specific cells. Changes in the apparent cell volume were quantified over a period of several minutes to obtain dehydration curves associated with exposure to concentrated extracellular electrolytes. The Kedem-Katchalsky coupled flow transport model was statistically fit to the data using a personal computer. Values for the permeability coefficients were adjusted to optimize the correlation between the theory and the data. An activation energy of 44.8 kJ/mol and a water permeability of 0.035 micron (atm.min) at 0 degrees C were derived from the data measured over a temperature range from -2 to -9 degrees C.

Animals↗

Emergency treatment of burn injury.

Emergency physicians often encounter patients who have suffered burn injuries. Most are minor in nature but approximately 100,000 a year are true emergencies. Regardless of severity, the emergency physician and staff must possess the evaluative skills and knowledge of current treatment regimens to appropriately treat these patients. Burn injuries are classified according to extent of body surface involved and depth of skin injury. This classification, together with an understanding of the pathophysiology based on the source of injury, will allow categorization and thereby determine initial therapy and definitive management. The treatment of minor burns focuses on three primary objectives: relief of pain, prevention of infection and additional trauma, and minimizing of scarring and contracture. With major burns the first hours after injury are characterized by life-threatening problems. Airway injuries, trauma other than the burn injury, treatment of shock, and pain relief are of the highest priority, overriding the management of the burn wound itself. The care that the minor burn victim receives is critical to ultimate outcome; the care that the major burn victim receives is critical to both immediate survival and ultimate outcome. The emergency physician must provide optimal care to ensure optimal results.

Burns↗

The effect of burn wound excision on measured energy expenditure and urinary nitrogen excretion.

The effect of wound closure on the metabolic response to burn injury is uncertain. Energy expenditures were measured in 20 patients by indirect calorimetry (MEE) and estimated initially by the Curreri formula (CEE) and subsequently by a modification of the Curreri formula (MCEE), adjusted for changes in open wound size and body weight. Urinary urea nitrogen (UUN) excretions were measured over 24 hours. Second- and third-degree burns, initially involving 31% to 74% of the body surface areas, were reduced in size to less than 15% by excisions and grafting procedures. The correlations among percentage open wounds, MEE's, CEE's, and MCEE's were low. UUN excretions were not correlated with percentage open wounds or with MEE's. Estimates of energy expenditures using the Curreri formula appear to be of limited usefulness in prescribing caloric intakes in burned patients. Serial UUN's are useful in determining protein requirements, but were not correlated with MEE's or with the extent of open wounds.

Adolescent↗

Effect of burn trauma on adrenal and testicular steroid hormone production.

The effects of burn trauma in men on the production of adrenal and testicular steroids was investigated. Whereas there were significant increases in serum cortisol levels and urinary 17-hydroxycorticosteroid excretion soon after thermal injury, there were significant decreases in serum dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, and testosterone concentrations during the first 4 weeks following burn trauma. Serum androstenediol and androstenediol sulfate levels also were reduced, though insignificantly, 10-23 days postburn. Serum LH levels were unchanged during the postburn interval. Since urinary 17-ketosteroid excretion was normal or below normal rather than increased, the decline in serum C19-steroid levels probably resulted from decreased glandular secretion rather than increased rates of metabolism and excretion. Low dehydroepiandrosterone sulfate and/or testosterone levels were found in some men several months after recovery from their burns. These data suggest that thermal injury leads to acute inhibition of adrenal and testicular C19-steroid secretion, but stimulation of adrenal glucocorticosteroid production, and that endocrine function in many instances is not normalized after complete healing of the burned surfaces. The mechanisms and physiological consequences of such changes in the steroid milieu of men after burn trauma are unknown.

17-Hydroxycorticosteroids↗

Metabolism and nutrition in burned patients.

The hypermetabolic and protein-wasting syndrome of burn injury is quantitatively the most severe and prolonged encountered in acute surgical diseases. It demands nutritional care to minimize the multiple complications of malnutrition. Nutritional support today is aimed at a daily administration of calories between 1.37 and 1.7 times the basal metabolic rate with 20% or more of these calories as protein. Fat emulsions are used twice weekly to replace essential fatty acids. Vitamins, minerals, and trace metals are supplied regularly. Current recommendations can be made based on a decade of experience, but they are changing rapidly with increased knowledge of the metabolic abnormalities occurring in the burn patients and on experience with a decade of nutritional replacement.

Burns↗

Current concepts in burn care.

The understanding of and care for burn trauma have become increasingly sophisticated. A review of important clinical and laboratory conditions over the past five years highlights current thought and future trends in burn management.

Burns↗

Stimulation of renin secretion by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8).

The intracellular calcium antagonist 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) prevents the release of Ca2+ from cell storage sites. The effect of this compound on renin secretion from rat renal cortical slices in vitro was investigated. TMB-8 was a potent stimulant of renin secretion within the concentration range 10(-5)M to 5 X 10(-4)M with an optimum concentration of 2 X 10(-4)M. TMB-8 overcame the inhibition of renin secretion by angiotensin II, ouabain, 60 mM KCl and A23187. The results add to the existing evidence that Ca2+ is a common inhibitory messenger for a number of compounds which affect renin release and suggest a role for intracellular calcium stores in the regulation of juxtaglomerular cell Ca2+ levels.

Animals↗

Failure of local immunity. A potential cause of burn wound sepsis.

Destruction of the skin barrier by thermal injury removes the major local defense barrier to bacteria. To determine whether a local defect in immunity also existed, the opsonic activity of blister fluid against Staphylococcus aureus and Pseudomonas aeruginosa as well as neutrophil chemotaxis were measured. The results of these studies indicated that blister fluid could not opsonize Pseudomonas. A series of repletion experiments indicated that the opsonic defect for Pseudomonas was not due to the presence of inhibitors but was due to the lack of normal serum factor(s). Although both the level of immunoglobulins and complement components in the blister fluid was depressed, the cause of the opsoninopathy appeared to be due to local consumption of complement in the burn wounds. In addition to the opsoninopathy, both neutrophil chemotaxis and random migration were also depressed. In conclusion, a burn injury appears to cause severe impairment of both cellular and humoral local immunity, which could predispose these patients to burn wound sepsis.

Adolescent↗

Reduction of intrinsic contractile reserves of the left ventricle by Escherichia coli endotoxin shock in guinea-pigs.

To test the hypothesis that cardiodynamic responses during endotoxemia are limited by intrinsic myocardial dysfunction, we studied contractile properties of isovolumic left ventricular (LV) preparations isolated from E. coli endotoxin-shocked guinea pigs. Compared to control hearts, shock hearts developed significantly lower LV systolic pressures (54 +/- 7 v. 84 +/- 2 mmHg; P less than 0.001) and maximal rates of LV pressure rise (+dP/dtmax; 886 +/- 106 v. 1246 +/- 39 mmHg/s; P less than 0.006) and fall (-dP/dtmax; 702 +/- 98 v. 1103 +/- 26 mmHg/s; P less than 0.001). The LV mechanical disadvantage of shock hearts was not correlated with changes in beating frequency, active state duration, or tissue water content; neither was it surmounted by pyruvate nor by maximally effective increases in coronary flow, diastolic stretch, or extracellular Ca2+ concentration. These findings suggest that endotoxin pathogenesis encompasses a decrease in intrinsic contractile reserves of the left ventricle, and that the resulting changes in myocardial contractile mechanisms may underlie cardiac involvement in endotoxin shock syndromes.

Animals↗

Predicting energy expenditures in burned patients.

Daily caloric requirements in patients with major burns are frequently estimated using the Curreri formula (25 X body weight (kg) + 40 X % BSA burned). In nonburned patients modifications of the Harris-Benedict formulas have been used to estimate energy requirements. These equations have not been validated against measured energy expenditures in burned patients. Thirty-five patients with second- and third-degree burns covering from 10 to 75% of the body surface area underwent assessments of energy expenditures by indirect calorimetry and by the Curreri and Harris-Benedict formulas. The mean energy expenditure calculated from the Harris-Benedict formulas (BEE) underestimated the mean measured energy expenditure (MEE) by 23% (p less than 0.001), while the mean energy expenditure calculated from the Curreri formula (CEE) overestimated the mean MEE by 58% (p less than 0.001). There were significant correlations between the MEE, BEE, and CEE. In patients with burns greater than 20% of the body surface area, the correlation between MEE and BEE was higher than that found with the Curreri formula.

Adolescent↗

Burns in motor vehicle accidents.

Burns received as a result of motor vehicle accidents (MVA's) create special problems in their care, as they are frequently severe and are often associated with other injuries. One hundred seventy-eight consecutive patients with burns sustained in an MVA were studied. The mean TBSA burn was 33.9%. The mortality was 24.7%, but the mean burn size in this fatal group was almost doubled at 63.9%. The injury most commonly associated with death was inhalation injury (in 36.3%). Thirty-six per cent of the patients sustained other injuries in addition to their burn, the most frequent of which was to the musculoskeletal system (67 injuries). Multiple trauma had little effect on mortality unless severe, but fractures especially complicated burn wound care unless surgically stabilized. Current methods of management are presented along with our approach to multiply injured burn patients.

Accidents, Traffic↗

Divergence in adrenal steroid secretory pattern after thermal injury in adult patients.

The influence of thermal injury on adrenal secretion of dehydroepiandrosteron sulfate (DS) and cortisol was investigated in 19 adult patients. We found that within the first 5 days after burn trauma serum levels of DS were reduced to about one third the concentration in 21 similarly aged, nonstressed adults; serum cortisol levels in burned subjects were increased twofold over control levels. Serum DS levels were progressively lower, whereas serum cortisol concentrations remained relatively constant in burned patients between 6 and 55 days postburn. These data demonstrate prolonged alterations in adrenal steroid production after thermal injury and are suggestive that adrenal androgen production is, at least in traumatized subjects, regulated by factors other than ACTH.

Adolescent↗

Composite skin graft: frozen dermal allografts support the engraftment and expansion of autologous epidermis.

Rapid closure of burn wounds significantly reduces the complications associated with thermal injury. Successful wound coverage, however, is often limited by the lack of suitable autografts. To circumvent this limitation a composite graft was developed which combines the utility and availability of allogeneic skin with the permanence of an autograft. Composite grafts were first employed in a rat wound model and subsequently to treat six patients with thermal injuries. In experiments with rats, full-thickness excised (1") wounds were prepared on thoracic walls, covered with previously frozen allograft skin, dressed, and secured. Five days later, the dead epidermis was removed and trypsin-disaggregated syngeneic epidermal cells applied to the exposed dermal surface. Successful engraftment with complete epidermal coverage could be observed within 7 to 10 days. In eight patients, split-thickness skin bank allografts were placed on full-thickness burn wounds. Four days later the dead epidermis was removed and vacuum blister-prepared sheets of autologous epidermis grafted to the exposed dermal surface. In all eight patients successful engraftment ensued. Increased pigmentation at the site of each original epidermal graft confirmed the stability of underlying allograft dermis. Epidermal expansion ranged from 1:20 to 1:100. All patients were followed from 10 to 12 months with no demonstrated graft loss or significant wound contracture. Composite skin grafts which combine allogeneic dermis and an expanded autologous epidermis can effect rapid wound closure and will remain stable without evidence of rejection or graft breakdown for at least 12 months.

Adolescent↗

Decreased contractility and compliance of the left ventricle as complications of thermal trauma.

To test the hypothesis that systemic complications of dermal burns encompass dysfunction of myocardial contractile mechanisms, we studied contraction-relaxation properties of isovolumic left ventricular (LV) preparations isolated from guinea pigs 24 hours after full-thickness burn to approximately 47% total body surface area. Compared to control hearts, hearts from burned subjects consistently generated significantly lower values for LV systolic pressure (94 +/- 2 vs 66 +/- 2 mm Hg; p less than 0.001) and maximal rates of LV pressure rise (+ dP/dtmax; 1296 +/-71 vs 1091 +/- 46 mm Hg X sec-1; p less than 0.05) and fall (-dP/dtmax; 1214 +/- 45 vs 856 +/- 34 mm Hg X sec-1; p less than 0.001). The LV contractile deficit of burn hearts was not correlated with changes in tissue water content, and it was not surmountable by excess glucose, insulin, increased coronary flow, or maximal preload elevation. In addition, end-diastolic pressure-volume relationships in burn hearts were shifted upward and to the left of controls in the direction of decreased compliance (p less than 0.05 to p less than 0.01). Thus, LV sequelae of thermal trauma manifest in isolated hearts as decreased contractility, slowed isovolumic relaxation, and decreased diastolic compliance; in the intact animal this combination would reduce ejection and impede filling of the ventricle, with diastolic pressures reflecting changes in compliance as well as in contractile function.

Adenosine↗

Stimulation of renin release from rat renal cortical slices by cyclosporin A.

Cyclosporin A is known to produce increases in plasma and kidney renin in vivo. In this study, Cyclosporin A was shown to stimulate renin release in vitro in rat renal cortical slices. At the optimal concentration of 8 x 10(-6) M Cyclosporin A, renin release was stimulated by up to 43% during a 2 hr incubation at 37 degrees. This observation strengthens the hypothesis that the intra renal renin-angiotensin system may participate in the mechanism of Cyclosporin A nephrotoxicity.

Animals↗

Contractile function and rhythmicity of cardiac preparations from Escherichia coli endotoxin-shocked guinea pigs.

Isovolumic left ventricular (LV) preparations were isolated from guinea pigs 16-18 hr after IP injection of either saline (control groups) or 4 mg/kg of Escherichia coli endotoxin (shock groups). The tissues were then subjected to mechanical performance comparisons in a carefully regulated coronary perfusion system. Endotoxicosis consistently resulted in myocardial contractile dysfunction as evidenced by significantly low values for LV systolic pressure and maximal rates of LV pressure rise (+dP/dtmax) and fall (-dP/dtmax). There was a distinct tendency for spontaneous tachybradydysrhythmias in the shock groups, but the LV contractile deficit was not dependent upon beating frequency. Also, LV function curves (systolic pressure vs end-diastolic pressure) generated by shock hearts were shifted downward and to the right of control curves, in the direction of inotropic failure. Thus, cardiodynamic adjustments during endotoxin shock may reflect and be limited by underlying dysfunction intrinsic to the heart itself; by 16-18 hr, the resulting functional changes in LV myocardium are manifested in an isolated environment and do not depend on depressive constraints operative in the intact host.

Animals↗

Cyclosporin A and renal prostaglandin biosynthesis.

The effect of cyclosporin A (CyA) treatment of rats on prostaglandin synthesis in the renal cortex was studied. Renal cortical slices were prepared from control and CyA-treated rats and the release of prostaglandins into the medium during incubation at 37 degrees was measured. Rats killed 4 hours after receiving 100 mg/kg CyA orally showed no changes in renal slice release of PGE2, PGF2 alpha, 6-keto-PGF1 alpha or thromboxane B2. The slice release of 6-keto-PGF1 alpha was tested after 5 days of CyA treatment and again there was no difference from control rats. The effect of CyA added to slice incubations in vitro was examined: CyA had no effect on PGE2 or 6-keto-PGF1 alpha release in the presence or absence of angiotensin II. Under all of these experimental conditions there was evidence of CyA-induced stimulation of the renin-angiotensin system. Indomethacin treatment did not inhibit CyA-mediated accumulation of renin in the renal cortex. The results suggest that renal prostaglandins do not play a role in CyA-stimulated renin storage or release, or in CyA nephrotoxicity.

6-Ketoprostaglandin F1 alpha↗

Effect of circulating fibronectin on stimulation of leukocyte oxygen consumption and serum opsonizing function in burned patients.

In a study of 27 thermally burned patients (mean TBSA, 58%; range, 32-96%) serum fibronectin levels were decreased with parallel decreased oxygen consumption of stimulated peripheral blood phagocytes and decreased EGTA-blocked burn serum opsonizing activity which correlated with serum fibronectin changes postburn. Normal and burn sera fibronectin content also correlated with the opsonizing times for zymosan and Staphylococcus aureus but not for Enterobacteriaceae. Although in vivo 14 cases showed circulating fibronectin 140 micrograms/ml or lower and a marked decrease in Staphylococcus aureus opsonization, only two patients from this group revealed positive Staphylococcus aureus blood cultures and serum fibronectin levels were higher in patients with Staphylococcus aureus sepsis than in patients with Enterobacteriaceae sepsis. Supplementary experiments on leukocyte oxidative response after zymosan stimulation in normal, fibronectin-depleted, and fibronectin-reconstituted serum demonstrated that the lag period of oxygen burst is a fibronectin-dependent reaction.

Adolescent↗