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Biomedical subjects

B A Pruitt

Publications and source records attributed to B A Pruitt.

At least 73 records · Page 4Linked to original sources

Plasma cytokines after thermal injury and their relationship to infection.

OBJECTIVE: The relationship of plasma cytokine levels to infection, core temperature, and to one another in patients with thermal injury was examined. SUMMARY BACKGROUND DATA: The response to infection has been associated with cytokines such as interleukin 1 beta (IL1 beta), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF alpha), and these cytokines have been studied in various inflammatory diseases. The authors previously reported that patients with thermal injury have elevated IL1 beta and IL6 plasma levels and that these cytokines may play different roles in the response to thermal injury. METHODS: IL1 beta, IL6, and TNF alpha were measured by enzyme-linked immunosorbent assay (ELISA) in serial samples of plasma from 27 patients. RESULTS: IL6 and TNF alpha levels were increased in severely infected patients as compared to patients who remained free of infection, and the IL6 level was higher in infected patients who died than those who survived. There was no apparent relationship between IL1 beta levels and infection. IL6 and IL1 beta were positively correlated with core temperature. The correlations between IL6 and IL1 beta, between IL6 and TNF alpha, and between TNF alpha and IL1 beta were significant. CONCLUSIONS: These results suggest that IL6 and TNF alpha play a role in the response of burned patients to infection.

Adult↗

Decreased pulmonary damage in primates with inhalation injury treated with high-frequency ventilation.

OBJECTIVE: This study compared two forms of high-frequency ventilation (HFV) with conventional volume ventilation (CON) in a primate model of inhalation injury to determine whether ventilatory mode was a determinant of pulmonary damage. SUMMARY BACKGROUND DATA: The authors previously reported that the prophylactic use of high-frequency flow interruption in patients with bronchoscopically diagnosed inhalation injury requiring mechanical ventilatory support resulted in a significant decrement in mortality. They hypothesized that a reduction in ventilatory mode induced pulmonary damage was in part responsible for their clinical results. METHODS: Fifteen adult baboons were randomized to one of three ventilatory modes (CON, high-frequency flow interruption [HFFI], or high-frequency oscillatory ventilation [HFO]) after moderate smoke injury. Ventilatory support was tailored to the same physiologic endpoints. After 7 days, the animals were killed and pulmonary pathologic changes were scored and compared. Repetitive physiologic and biochemical data were compared using analysis of variance for repeated measures. RESULTS: Physiologic endpoints were achieved in CON and HFFI, but not in HFO. Hemodynamic variables did not differ between CON and HFFI. The barotrauma index was greater in CON compared to HFFI (p < 0.05), despite similar PO2, FIO2, AA gradient, and PCO2. Animals treated with HFFI had significantly less parenchymal damage than those treated with CON (p = 0.03) or HFO (p = 0.0008). CONCLUSIONS: The prophylactic use of HFFI led to a significant decrement in ventilatory mode induced pulmonary damage and offers an explanation for the decreased mortality in inhalation injury patients treated with HFFI.

Animals↗

A rabbit model of inhalation injury.

In the course of developing a model of inhalation injury, the relationship between the severity of pulmonary injury and specific techniques and doses of smoke exposure was examined in pairs of rabbits simultaneously exposed to smoke. In group I (5 pairs), one animal in each pair was exposed to smoke with a breath hold (BH) at the end of each exposure; the second animal received an exposure producing the same level of carboxyhemoglobin without BH. In group II (6 pairs), both animals were exposed to 25 units of smoke simultaneously, with BH. In group III (3 pairs), one animal received a 20-unit exposure and the other a 25-unit exposure, both with BH. In group IV, 9 animals received 25-unit exposures with BH and were observed for 4 days. Groups V and VI served as controls. Smoke exposure with BH regularly produced severe injury in terms of decreased PaO2 and histopathologic changes, while exposure without BH did not, despite high levels of carboxyhemoglobin after smoke inhalation. The mean differences in percent residual PaO2 (PaO2 at 48 hours x 100/pre-injury PaO2) and in extravascular lung water (EVLW) at 48 hours within pairs of animals receiving 25 units with BH were 12.3% +/- 5.33%, and 0.271 +/- 0.157 mL/g, respectively. Histologic findings such as necrotic tracheobronchitis with pseudomembrane were consistently present. No differences were observed between animals receiving exposure of 20 and 25 units. During the 4 days of observation, three animals in group IV died. PaO2 was lowest on the second day and rose thereafter in all surviving animals except in one that had massive pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Kinetics of nitrogen oxide production following experimental thermal injury in rats.

Nitric oxide is biosynthesized from the amino acid L-arginine by the enzyme nitric oxide synthase. Nitric oxide is a vasodilator, a neurotransmitter, and may modulate immune function. The experiments presented here were performed to determine whether the synthesis of nitric oxide is increased following experimental burn injury in rats. After a 30% total body surface area burn in 300-g Lewis rats, the urinary output of nitrate, a stable metabolite of nitric oxide, was significantly increased for 8 days postburn compared with that in sham-burned control rats. The origin of the urinary nitrate from L-arginine was demonstrated by administering the stable isotope 15N2-guanido-arginine to burned and sham-burned rats and observing an immediate enrichment of 15N in nitrate. The amount of administered 15N recovered as 15NO3 was < 1% of the administered arginine isotope in both the burned and unburned rats; the recovery of the isotope increased tenfold over baseline recovery in burned rats. The arginine analog N-monomethyl-arginine, an inhibitor of the enzyme nitric oxide synthase, blocked the postburn rise in urinary NO3 output in burned rats, but did not completely inhibit the output of NO3 in burn wound-infected rats. Experimental burn injury in rats results in an increase in L-arginine-dependent nitric oxide production and urinary nitrate output.

Animals↗

The renal effects of low-dose dopamine in thermally injured patients.

The renal effects of low-dose dopamine (LDD) therapy in hyperdynamic thermally injured patients are unknown. We investigated the renal effects of LDD in ten burn patients (mean +/- SEM age and % total body surface burned: 30.2 +/- 3.3 years and 53.4% +/- 7%) and six controls (mean age; 20.2 +/- 0.5 years). Administration of LDD significantly increased glomerular filtration rate, effective renal plasma flow, sodium excretion, and urine flow in the controls and effective renal plasma flow, urine flow, heart rate, and cardiac index in the patients. The chronotropic effect of dopamine appears to be a principal contributor to the patients' increased effective renal plasma flow. Sodium excretion was increased by LDD only in the patients in whom the predopamine sodium excretion exceeded 5 mEq/h. Lack of a consistent natriuretic effect and the consistent chronotropic effect suggest that the routine use of low-dose dopamine in burn patients is unwarranted. The side effects that attend the desired response determine clinical use, i.e., the potential for blood flow redistribution and increased cardiac work demands must be balanced against increased renal plasma flow and natriuresis.

Adult↗

Plasma cytokines following thermal injury and their relationship with patient mortality, burn size, and time postburn.

We measured plasma levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) following thermal injury. Cytokine levels in the plasma of 27 burned patients were serially screened by ELISA and compared with cytokine levels in 16 healthy laboratory employees. The relationships between cytokine concentrations and patient mortality, burn size, and time postburn were examined. Plasma samples with detectable amounts of IL-1 beta and IL-6 were significantly more frequent in burned patients than in controls, whereas TNF alpha was undetectable in most plasma samples. All nonsurviving burned patients had detectable IL-6 levels; these were significantly higher than those of surviving patients. The IL-1 beta and IL-6 concentrations were highest during the first week after injury and declined over time. The IL-1 beta concentrations were positively correlated with burn size. These findings suggest that IL-1 beta and IL-6 may influence metabolic and immunologic responses in the first few weeks following thermal injury. Tumor necrosis factor alpha was transiently elevated in a small subpopulation of burned patients with no obvious relationship to burn size or time postburn.

Adult↗

Superior mesenteric artery syndrome in a burn patient.

Weight loss resulting from the hypermetabolic response to burn injury is not unusual and is often unavoidable. The loss of retroperitoneal fat has been postulated as a major factor in the cause of the uncommon complication of superior mesenteric artery syndrome. This syndrome is frequently treated nonoperatively with aggressive nutrition support. Nasojejunal feeding past the point of obstruction should be considered as the primary method of nutrition support. Alternatively, total parenteral nutrition or a combination of enteral and parenteral feeding may be necessary to meet nutritional needs until the duodenal obstruction resolves. This case study describes the nutrition management of a burn patient who developed superior mesenteric artery syndrome.

Burns↗

Wound closure and outcome in extensively burned patients treated with cultured autologous keratinocytes.

Cultured autologous keratinocytes (CAK) have been heralded as a means to achieve more rapid closure of massive burn wounds. Despite the claimed benefits of this technology, we have failed to identify its positive impact on wound closure in extensively burned patients. Sixteen patients with a mean age of 29.7 years (range, 10-56 years) and a mean total body surface area burn of 68.2% (range, 42%-85%) underwent 22 applications of CAK supplied by a private laboratory. The keratinocyte grafts were applied to a mean of 15.9% of the body surface area (range, 4%-59%) at an average cost per patient of $43,705 (range, $9,800 to $161,000). The mean body surface area of definitive wound coverage by these grafts was 4.7% (range, 0%-18.6%). The mean length of hospitalization was 132 days (range, 50-275 days). The observed mortality was 12.5% (two patients). Our experience with this wound care approach has been assessed with respect to the extent of burn, the level of wound excision, and the site of CAK application.

Adolescent↗

Alterations in intestinal permeability after thermal injury.

Alterations in intestinal permeability have been postulated to occur after thermal injury. We evaluated the status of intestinal permeability during the first 2 postburn weeks in 15 subjects by measuring the differential excretion of enterally administered lactulose and mannitol. The mean age and burn size of the patients were 32.7 +/- 3.6 years and 53.3% +/- 5.1% of the total body surface area, respectively. Ten healthy volunteers were also studied. The lactulose-mannitol excretion ratio was 0.159 +/- 0.017 for the patients and 0.017 +/- 0.003 for controls. The increased ratio did not correlate with burn size or postburn day. Patients who developed significant clinical infections during their first 2 postburn weeks had lactulose-mannitol ratios on postburn day 2 that were significantly higher than those of controls and patients who did not develop infections. This suggests a relationship between susceptibility to infection and early alterations in intestinal permeability.

Adult↗

Decreased wound contraction with fibrin glue--treated skin grafts.

Skin grafts can be used effectively to inhibit wound contraction. A critical element of this inhibition is the adherence of the graft to the wound bed. Fibrin glue has been shown to increase the adherence of skin grafts to wound beds. We therefore devised an experiment to determine the effect of fibrin glue on skin graft inhibition of wound contraction. Two 2.5 x 2.5-cm full-thickness defects were created on the dorsa of 15 Sprague-Dawley rats. Thirty partial-thickness grafts were harvested from isogeneric donor animals using a brown dermatome. Prior to grafting, one full-thickness defect, each animal received 0.2 mL of fibrin glue (Immuno AG, Vienna, Austria). The adjacent wound served as the control and received 0.2 mL of normal saline. Grafts were applied, sutured, and protected with an occlusive dressing. The size of graft sites treated with fibrin glue or normal saline was determined at the time of graft application and thereafter at 3-day intervals for 21 days using standardized photographic techniques. The percentage of change from initial wound size at each point was recorded for each group. Graft sites treated with fibrin glue contracted less than the controls from the ninth postgraft day to the completion of the study. The mechanism by which fibrin glue inhibits wound contraction may be related to increased adherence of grafts to the underlying wound bed. As an adjunct in skin grafting, fibrin glue may offer certain advantages that are not achieved by suturing alone.

Animals↗

The effect of elevated levels of thromboxane on host response to tumor.

Previous studies have demonstrated that human malignancies can synthesize large amounts of thromboxane. It has also been reported that thromboxane can significantly alter multiple components of physiologic and immunologic function. We investigated the effect of elevated levels of thromboxane on host response to tumor using multiple rat models, and the long acting thromboxane analogue U-46619. Administration of the thromboxane analogue was not found to significantly alter the growth of primary tumors or peritoneal metastases. The analogue was found to significantly decrease mean survival time with a pulmonary metastases model. The thromboxane analogue failed to alter macrophage cytotoxicity, lymphocyte cytotoxicity, T lymphocyte subset numbers, or lymphocyte blastogenic response. Administration of the thromboxane analogue decreased the rate of lymphocyte metabolism of glucose and decreased lymphocyte intracellular adenosine deaminase activity. In conclusion, elevated thromboxane levels do not appear to alter primary tumor growth or host immune function, but do decrease resistance to pulmonary metastases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Burns in morbidly obese patients.

It has been estimated that 26% of Americans are obese. A very small subset of this group can be categorized as morbidly obese, fulfilling the criteria of being 100 pounds, or 100%, over ideal body weight. The clinical records of seven morbidly obese burn patients treated over a 20-year period are reviewed. Particularly notable was a 43% incidence of fatal pulmonary embolism.

Adult↗

Identification of neopterin as a potential indicator of infection in burned patients.

Several fluorescent substances are present in the supernatants of acid-precipitated whole blood or plasma from burned patients. Perchloric acid supernatants of sera from infected, but not uninfected, burned rats contained a fluorescent substance with maximum emission at 420 nm at 355-nm excitation (355 ex/420 em). In this study of serum from burned human patients, several fluorescent substances were resolved by reverse-phase high-pressure liquid chromatography. One of these fluorescent components had an high-pressure liquid chromatography retention time and fluorescent characteristics identical to those of neopterin. The identification of this component as neopterin was verified by thermospray mass spectrometry. Serum neopterin concentrations were then determined in supernatants of patient serum samples having various levels of 355 ex/420 em fluorescence. A correlation was found between the concentrations of neopterin determined by high-pressure liquid chromatography and the presence of bacteremia in burned patients. These findings suggest that neopterin, which is a useful indicator of infection in other clinical settings, may also be an indicator of infection in burned patients.

Biopterins↗

Granulocyte oxidative activity after thermal injury.

BACKGROUND: Alterations in granulocyte function after thermal injury have been described. We have serially studied the level of granulocyte cytosolic peroxidase activity in 23 thermally injured patients during the first 6 weeks after injury. The patients' mean age and burn size were 35.1 +/- 15.7 years and 41.6% +/- 16.8% (range, 18% to 88%), respectively. Fourteen patients had concomitant inhalation injury, and the overall mortality rate was 4.3%. METHODS: Purified granulocytes were obtained from peripheral blood after red cell lysis and Ficoll-Hypaque (Pharmacia Inc., Piscataway, N.J.) gradient separation. Cells were loaded with dichlorofluorescin diacetate, and baseline fluorescence was measured by flow cytometry. After phorbol myristate acetate stimulation, fluorescence was measured again. Cells from unburned normal subjects were used as daily controls. RESULTS: The data are expressed as percent of stimulated control granulocyte fluorescence. Unstimulated patient granulocytes demonstrated a significantly higher baseline activity than did unstimulated controls (22.9% vs 15.4%; p < 0.05). Mean fluorescence from stimulated granulocytes was 114% of the control values (p < 0.05). CONCLUSIONS: Granulocytes from thermally injured patients exhibited a baseline increase in cytosolic oxidase activity, suggesting in vivo activation and a greater than normal oxidase activity after in vitro stimulation.

Adult↗

The effects of platelet-activating factor (PAF) and a PAF antagonist (CV-3988) on smoke inhalation injury in an ovine model.

The role of platelet-activating factor (PAF) in inhalation injury was studied in sheep, using CV-3988, a PAF antagonist. Following smoke exposure, 15 sheep were divided into three groups of five. Group I animals were untreated; group II animals were treated with CV-3988 before and after exposure; group III animals were treated only after exposure. In group I, platelet and WBC counts were markedly changed within 6 hours (p less than 0.05); in the treated groups, alteration of cell counts was not obvious. Blood malondialdehyde (MDA) levels were increased significantly only in group I. Blood PGE2 and TXB2 levels did not differ among the groups. Mean tissue MDA and mean bronchoalveolar lavage fluid (BALF) MDA concentrations were significantly increased in group I (p less than 0.01); mean BALF TXB2 levels were significantly decreased in group I (p less than 0.01). These data suggest that PAF affects inhalation injury through modulation of lipid oxygenation and that PAF antagonists may offer therapeutic benefit in the management of this injury.

Animals↗