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Biomedical subjects

C R Baxter

Publications and source records attributed to C R Baxter.

At least 19 recordsLinked to original sources

Liposome delivery of aminoglycosides in burn wounds.

The current study evaluated the pharmacodynamics of topically applied antimicrobials incorporated into radiolabeled liposomes. Radiolabeled 125I-phenyldecanoic acid was used in the formulation of small unilamellar liposomes. Sephadex (cross-linked dextran beads) G-50 columns were run to determine the per cent of radioactivity incorporated into liposomes and persistence of radioactive tag on the liposome after two weeks (greater than 95 per cent) remained incorporated. On the day of the experiment, 31 adult Sprague Dawley rats were subjected to a 10 per cent total body surface area full thickness burn (Walker burn model). All rats were treated with topical application of 0.3 milliliters of tobramycin entrapped in 125I-liposomes, and burn wounds were covered with Opsite (Winfield Laboratories). This formulation resulted in each rat receiving 14 milligrams per kilogram of tobramycin with a specific activity of 10.41 microcuries. Rats were sacrificed at several time periods after burn injury (nine after 24 hours, 12 after 48 hours, 11 after 72 hours). At these time intervals, serum and tissue tobramycin levels were measured, burn dressing, burn tissue and splanchnic organs were harvested and radioactivity was assessed with a gamma scintillation counter to determine tissue concentration of 125I-liposome tobramycin. Concentration of tobramycin in the serum was negligible at 24, 48 and 72 hours postburn, but was significant in the burn tissues at these times. The radioactive recovery data demonstrated that the majority (greater than 90 per cent) of the recovered liposomes remained at the site of application (the burn wound). No splanchnic organs had greater than 2 per cent of the recovered 125I-liposomes at any time period. These data suggest that, in burn wounds, tobramycin incorporated into liposomes remain at the site of initial application, resulting in high local concentrations with little systemic absorption and confirm that liposomes provide an effective vehicle for delivery of antimicrobials at the site of the burn injury.

Animals

Nutrition for adult burn patients: a review.

Adequate nutritional support is an important aspect of burn therapy. To accomplish this goal, nutrition assessment must be conducted, with particular attention given to the determination of energy and macronutrient needs. Providing these nutrients by the enteral route is recommended.

Adult

Topical liposomal delivery of antibiotics in soft tissue infection.

A new drug delivery system (lipid microcarriers) was studied in an experimental model of infected soft tissue wounds. Superficial, nonlethal infection was produced in the adult rat by injecting 1 ml containing 10(8) colony-forming units (CFU) of Pseudomonas aeruginosa under the superficial fascia of the paraspinus muscle of a 2-cm2 excised wound. All wounds were dressed with N-Terface, a nonadherent wound material, and covered with Kontor sponge, an open-cell polyurethane sponge containing either normal saline (group I), free tobramycin (groups III and V), liposome-entrapped tobramycin (groups II and IV), silver sulfadiazene (group VI), or liposome-entrapped silver sulfadiazene (group VII). At 24, 48, and 72 hr postinjection, animals were sacrificed and colony-forming units of P. aeruginosa per gram of muscle tissue were determined. Group I had significantly higher colony-forming units of P. aeruginosa per gram than groups II and III at 48 and 72 hr and than groups IV and V at all times. One single dose of liposome-encapsulated silver sulfadiazine significantly decreased bacterial counts compared to untreated controls and, to a similar extent, compared to multiple applications of free drug. Colony-forming units in all treatment groups (II and III, IV and V, VI and VII) were similar at all time periods within equivalent dosages. The ability of one application of liposomal-entrapped antibiotics to result in a therapeutic effect that requires multiple applications of topically applied free antibiotics offers potential clinical advantages.

Administration, Topical

Hypertonic saline dextran resuscitation of thermal injury.

Burn treatment requires large volumes of crystalloid, which may exacerbate burn-induced cardiopulmonary dysfunction. Small-volume hypertonic saline dextran (HSD) resuscitation has been used for effective treatment of several types of shock. In this study isolated coronary perfused guinea pig hearts were used to determine if HSD improved left ventricular contractile response to burn injuries. Parameters measured included left ventricular pressure (LVP) and maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max) at a constant preload. Third-degree scald burns comprising 45% of total body surface area (burn groups, N = 75), or 0% for controls (group 1, N = 25) were produced using a template device. In group 2, 25 burned guinea pigs were not fluid resuscitated and served as untreated burns; 20 burns were resuscitated with 4 mL lactated Ringer's (LR) solution/kg/% burn for 24 hours (group 3); additional burn groups were treated with an initial bolus of HSD (4 mL/kg, 2400 mOsm, sodium chloride, 6% dextran 70) followed by either 1, 2, or 4 mL LR/kg/% burn over 24 hours (groups 4, 5, and 6, respectively). Untreated burn injury significantly impaired cardiac function, as indicated by a fall in LVP (from 88 +/- 3 to 68 +/- 4 mmHg; p = 0.01) and +/- dP/dt max (from 1352 +/- 50 to 1261 +/- 90 and from 1150 +/- 35 to 993 +/- 59; p = 0.01, respectively) and a downward shift of LV function curves from those obtained from control hearts. Compared to untreated burns, hearts from burned animals treated with LR alone showed no significant improvement in cardiac function. However hearts from burned animals treated with HSD + 1 mL LR/kg/% burn had significantly higher LVP (79 +/- 4 vs. 68 +/- 4 mmHg, p = 0.01) and +/- dP/dt max (+dP/dt: 1387 +/- 60 vs. 1261 +/- 90 mmHg/sc, p = 0.01; -dP/dt: 1079 +/- 50 vs. 993 +/- 59 mmHg/sc, p = 0.01) than hearts from untreated burned animals and generated left ventricular function curves comparable to those calculated for hearts from control animals. Mortality 24 hours after burn was 29% for untreated burns was 0% for control animals, as well as for groups treated with the Parkland formula or HSD plus 1 or 2 mL/kg/% burn lactated Ringer's. The only deaths after treatment occurred in those animals given HSD plus 4 mL/kg/% burn, Parkland formula (17% mortality).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Enhanced effectiveness of intraperitoneal antibiotics administered via liposomal carrier.

The local application of antibiotics to treat intraperitoneal contamination has been used with variable results. Liposomes are not rapidly absorbed from the peritoneal cavity, offering a potential delivery system for intraperitoneal antibiotics. The effects of liposome-incorporated antibiotic administration in a fecal peritonitis model were compared with the effects of conventional intraperitoneal and intramuscular antibiotics. Rats were divided into four groups: untreated, intramuscular cefoxitin, intraperitoneal cefoxitin, and intraperitoneal liposome-incorporated cefoxitin. Quantitative blood cultures were drawn at 4 and 24 hours. Liposome delivery of cefoxitin significantly reduced mortality and bacteremia at 4 and 24 hours compared with control subjects and conventional antibiotic groups. Peritoneal abscess formation tended to decrease in the liposome antibiotic group (mean +/- SEM, 6.86 +/- 0.79) compared with the group receiving free intraperitoneal administration of antibiotics (10.33 +/- 1.63). We conclude that liposomal delivery significantly enhances the effectiveness of cefoxitin in this model of peritonitis.

Animals

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

Surgical management of traumatic injuries of the right colon. Twenty years of civilian experience.

Three hundred seven patients with right colon injuries were treated at Parkland Memorial Hospital, Dallas, between 1953 and 1973. These injuries were managed with loop colostomies, suture and cecostomy, primary repair, right colectomy, diverting colostomy, and appendectomy or cecostomy alone. The indications and results of each type of repair are analyzed separately. The mortality (3.21%), morbidity (22%), and hospital stay were not related to the modality of treatment, but were influenced by the injuring agent. Adequate treatment of civilian right colon injuries implies careful individualization to avoid serious septic complications and subsequent mortality.

Adult

Early tangential excision and immediate mesh autografting of deep dermal hand burns.

Thermal injuries to the hand constitute not only one of the most common burns, but one of the most difficult for the burn surgeon to treat. Early wound closure is mandatory if maximum functional return is to be attained and scarring minimized. Over the last three and one-half years, 60 patients with deep dermal dorsal hand and finger burns were treated by tangential excision and immediate mesh autografting. All patients were admitted to the hospital within 24 hours of injury and excision was performed between the third to the tenth post burn day. Operative technique consisted of sequential eschar excision using the Humby knife or Goulian-Weck dermatome until viable dermis was visible. Mesh autograft, ratio 1 to 1(1/2) without expansion, was applied. There was 100% graft take in all but four hands. Hand function with full range of motion returned by the tenth postoperative day. Complications were minor. Patient follow-up ranged from six months to three and one-half years. No patient has required subsequent surgery for scar revision or contracture release. Range of motion in all patients has been excellent and all patients have continued to maintain normal hand function. The cosmetic appearance has been good except for the early "mesh" appearance of the graft which has become less apparent with time. In summary, early tangential excision and immediate mesh autografting of deep dermal dorsal hand burns has fulfilled the following burn principles-preservation of tissue, prevention of wound infection, maintenance of function and early wound closure.

Adolescent

The role of NADH-NADPH oxidase activity in the leukocyte function of burned patients.

Irreversible sepsis, in spite of advancements in topical therapy and antimicrobial agents, remains the leading cause of death in major thermal injury. A defect in intracellular bactericidal capacity in leukocytes from severely burned patients appears to correspond with increases in bacterial wound colonization and ultimate sepsis. This leukocyte defect has been demonstrated by abnormally low nitroblue tetrazolium reduction (NBT) and oxygen consumption of white cells in patients with major thermal injury. The subcellular mechanisms responsible for decreased bactericidal capacity were therefore investigated. Nicotinamide-adenine dinucleotide (NADH) and nicotinamide-adenine phosphodinucleotide (NADPH) oxidase activity was measured in patients with major burns, controls (normals), and in patients with nonburn stress or infection. NADH and NADPH oxidase levels in leukocytes from burn patients were not significantly different from those of normal nonchallenged controls but were significantly lower than the leukocyte values found in the patients with nonburn infections or stress. This NADH and NADPH defect in the subcellular leukocyte fraction suggests that it may be a significant factor in the reduced bactericidal function of the intact leukocyte in thermally injured patients.

Burns

Liquid propane cold injury: a clinicopathologic and experimental study.

A case of liquid propane cold injury is described. This injury was produced by evaporative heat loss, without ignition, from skin and underlying tissues. The cutaneous appearance was that of a flame burn but underlying deep tissue damage was present. Acute vascular compromise and progressive wound sepsis were complications which required surgical intervention. A liquid propane animal model was created which defined the pathophysiology of the clinical injury. The potential for this injury exists wherever volatile liquified gases are used.

Adolescent

Problems and complications of burn shock resuscitation.

The problems and complications of the fluid resuscitation phase of the treatment of major thermal burns are many and varied. Emphasis has been placed on the most important organ system responses commonly observed in the first week after injury. The efficacy of treatment and the lack of available treatment are outlined. The mechanical complications occurring from poorly selected and monitored fluid administration sites, complications of monitoring, problems of constrictive edema (usually in the extremities), airway problems, respiratory care, and innumerable other technical aspects were purposely omitted. While these problems and complications are extremely important and occur commonly in our experience, they are in the realm of technical performance of good emergency and intensive care medicine and their optimal management does not affect the problems and complications of the residual organ systems.

Adult

Use of the Y-body for identification of skin source on a successfully grafted burn patient.

The use of the interphase male Y-body (fluorescent Y chromosome segment) technique with cryostat sections of both fresh and frozen-stored skin biopsies is described. A female burn patient appeared to retain her donor homografts, thereby negating the need for autografts. Since a retained homograft of this sort challenged our understanding of immunologic barriers, we applied the Y-body technique to cutaneous biopsies obtained from the patient's burn area that had been homografted with skin from a male donor, as well as control biopsies from the patient's unburned skin and normal control male and female skin. Based on clinical and cytogenetic observations, it was concluded that the most reasonable explanation for this case was that the regenerating tissue at the graft site was that of the recipient and not that of the originally grafted male skin.

Burns

Characterization of elevated fibrin split products following thermal injury.

These studies establish that the staphylococcal clumping test is superior to the tanned red cell hemagglutination inhibition immunoassay for monitoring fibrin split product concentration in burn sera. It is strongly suggested that the principal circulating degradation product is a complex of soluble fibrin monomer with fragment D. Finally, there does not appear to be any effect on measured fibrin split product concentration in sera of burn patients receiving prophylactic heparin or aspirin.

Aspirin

Coagulation dynamics following thermal injury: effect of heparin and protamine sulfate.

A burned rat model was developed to examine post-burn alterations in coagulation. Fibrin split product concentration, as measured by the staphylococcal clumping test, was noted to rise significantly within the first 24 hours following injury. Prophylactic in vivo systemic anticoagulation with heparin was ineffective in modifying this response. However, systemic administration of protamine sulfate prevented post-burn elevation of fibrin split products. In vitro fibrin split product concentration in burn sera following the addition of heparin and protamine sulfate, was also analyzed. The results of these experiments elucidated the biochemical effects of protamine sulfate on circulating fibrin degradation products in the rat burn model.

Animals