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Biomedical subjects

J P Waymack

Publications and source records attributed to J P Waymack.

At least 55 records · Page 3Linked to original sources

The effect of ibuprofen on postburn metabolic and immunologic function.

Patients suffering severe trauma, including thermal injuries, demonstrate both a hypermetabolic response and an immunosuppressed state following the injury. Biochemically, these patients produce extremely large amounts of cyclooxygenase products, including prostaglandin E. We have investigated the effect of a drug, ibuprofen, which blocks the synthesis of prostaglandins in a burned rat model. Ibuprofen at high doses was found to significantly diminish the hypermetabolic response to burn injury and sepsis. The same dosage of ibuprofen increased the mortality rate in the same burn sepsis model. Prostaglandin E may therefore exert some beneficial effects in traumatized patients by altering their metabolism.

Animals↗

The effect of PGE in multiple experimental models. II. Effect on steady-state levels of plasma and brain amino acids and transmitters.

Elevations in prostaglandin E (PGE) have been documented in tumor and trauma patients. The physiologic significance of this elevation is not fully established. Utilizing a long-acting derivative of PGE, 16,16-dimethyl-prostaglandin E (dPGE), in a rat model, we evaluated its effects on metabolic rates, amino acid, and neurotransmitter metabolism. dPGE was not found to significantly alter resting metabolic rate. It did decrease the plasma level of three amino acids, including tyrosine. Although dPGE also decreased brain tissue levels of tyrosine, no significant alterations were observed on amine neurotransmitters or metabolites.

Amino Acids↗

Effect of prostaglandin E in multiple experimental models. VI. Effect on T-cell subsets.

Burn injuries have been shown to impair immune function. One of the hypotheses for the etiology of the immunosuppression is that burn injuries result in an elevation of prostaglandin E (PGE) levels which then impair leukocyte function. We evaluated the effect of PGE levels on immune function in multiple animal models utilizing T cell subset levels for our immunologic measurements. Elevations in PGE levels were achieved by administering 16,16-dimethyl-prostaglandin E (dPGE) and reductions by administering indomethacin. The animal models included burned rats, burned-septic rats, and nonburned rats. Neither indomethacin nor dPGE administration resulted in alterations of any of the T cell subset populations in our models.

16,16-Dimethylprostaglandin E2↗

A prospective trial of prophylactic intravenous immune globulin for the prevention of infections in severely burned patients.

A prospective randomized double-blind study evaluated the efficacy of i.v. immune globulin in preventing infectious complications in severely burned patients. Fifty patients were randomized to receive either i.v. immune globulin or placebo. Each group of patients was treated with twice weekly infusions for either 5 weeks or until the patients' wounds were covered. Patients treated with the immune globulin had an immediate correction of their depressed serum IgG levels, however there was no change in the infection or mortality rates. No adverse effects were noted with the immune globulin treatments. One potential weakness of this study was the greater burn surface area and a higher incidence of inhalation injury in adult patients treated with i.v. immune globulin compared to controls.

Adolescent↗

The effect of perioperative blood transfusions on long-term survival of colon cancer patients.

Blood transfusions have repeatedly been shown to decrease the rejection rate of transplanted organs by inducing an as yet undetermined form of immunosuppression. To evaluate whether these transfusions also decrease resistance to tumor metastases, records of patients who underwent colon cancer surgery were reviewed. A comparison was made between those who received perioperative transfusions and those who did not receive blood with regard to long-term survival. Patients receiving transfusions were found to have a significantly lower long-term survival rate than those who did not receive perioperative transfusions. This finding was most pronounced in those patients who had grossly localized disease at the time of surgery. The use of transfusions at the time of colon cancer surgery may therefore be detrimental to the patient's long-term prognosis.

Blood Transfusion↗

Alterations in host defense associated with inhalation anesthesia and blood transfusion.

Anesthesia and blood transfusions have been demonstrated to impair immune function. The present study evaluated whether these impairments led to increased susceptibility to infectious complications in two animal models. Both transfusions and anesthesia (methoxyflurane) were found to increase susceptibility to peritoneal Escherichia coli infections. This susceptibility increased with time after the transfusions but decreased with time after anesthesia. Neither transfusions nor anesthesia altered susceptibility to an intravenous Escherichia coli challenge in rats.

Anesthesia, Inhalation↗

Effect of prostaglandin E on immune function in multiple animal models.

The immunosuppression seen following major trauma and burns has long been attributed in part to prostaglandin E (PGE). This has been due primarily to the demonstration that PGE levels are elevated following burns and that when PGE is added to leukocyte cultures, it impairs multiple types of leukocyte functions. We investigated the effect of a new long-acting PGE derivative, 16,16-dimethyl-PGE, on immune function in multiple animal models. The PGE derivative had no effect on mortality in burn sepsis models but improved mean survival times in an Escherichia coli peritonitis model. The PGE derivative impaired neutrophil migration into burn wounds at lower dosages. In a rat burn model, when PGE was administered parenterally, it failed to impair cell-mediated immunity at any dosage and improved lymphocyte function at certain dosages. These data indicate that PGE may not be as immunosuppressive in in vivo models as it has been shown to be in in vitro models.

Animals↗

Effect of blood transfusions on immune function: IV. Effect on tumor growth.

Blood transfusions have previously been shown in retrospective studies of oncologic surgical patients to be associated with an increased incidence of tumor metastases and decreased long-term survival rate. The possibility that these findings were due to patients with larger, more aggressive tumors requiring the transfusions could not be excluded. To eliminate this possibility, the effect of transfusions on tumor growth in a rat sarcoma model was tested. In this study it was shown that allogeneic transfusions increase the rate of tumor growth and decrease mean survival times. This effect was not demonstrated when syngeneic transfusions were used. These data indicate that the diminished long-term survival seen in transfused patients undergoing tumor resection may be due to an impaired immunologic response to the tumor. Avoidance of this effect might be possible through the use of human syngeneic (autologous) transfusions.

Analysis of Variance↗

Carnitine supplementation vs. medium-chain triglycerides in postburn nutritional support.

The effect of dietary supplementation of carnitine on protein metabolism was studied in a burned guinea-pig model. Animals bearing a 30 per cent total body surface area burn were enterally infused with three isocaloric and isonitrogenous diets via gastrostomy feeding tubes for 14 days. Two diets contained safflower oil (long-chain triglycerides, LCT) and another diet contained medium-chain triglycerides (MCT) as their lipid sources (30 per cent of total calories as lipid). L-Carnitine was added to one of the two diets containing safflower oil. There were no significant differences in nitrogen balance, urinary excretion, serum albumin or transferrin among the three groups. However, the use of MCT in place of LCT appeared to increase liver weight and liver nitrogen. In this model, carnitine supplementation did not enhance the nitrogensparing effect of fat following burn injury.

Animals↗

A comparison of Biobrane vs. homograft for coverage of contaminated burn wounds.

An evaluation was made comparing homograft to Biobrane for the coverage of excised burn wounds using a rat model which had been contaminated with 1 x 10(5) Pseudomonas aeruginosa 1244. The homograft and Biobrane were then covered with either silver sulphadiazine cream, a 5 per cent mafenide acetate solution, or no topical antibacterial agent. Five days later the wounds were examined to determine the percentage of graft take. The homograft was found to have a superior graft take in this model. It is therefore recommended that a surgeon using Biobrane for the first time ensures the wound is at least as free of bacterial contamination as he would if he were using homograft.

Animals↗

Surgical correction of burn scar contractures of the foot in children.

The results of reconstructive procedures for the treatment of burn scar contractures of the feet in 55 children undergoing 90 operations were reviewed. The patients were treated in all but one case by release of the contracture band with placement of a skin graft in the resulting defect. There was an overall recurrence rate of 15 per cent that was not affected by the use of split-thickness versus full-thickness grafts. The time delay from the thermal injury to the reconstructive procedure was also found not to affect the outcome. Postoperative immobilization by the use of either a dynamic or an adynamic splint was found to be important both for preventing graft loss and for decreasing the rate of contracture recurrence.

Burns↗

Effect of blood transfusions on immune function. III. Alterations in macrophage arachidonic acid metabolism.

Blood transfusions have been shown to prevent allograft rejection, to increase the rate of tumor growth, and to increase susceptibility to infectious complications. We evaluated the mechanism of this immunosuppression by studying the effect of transfusions on macrophage function in a Lewis rat model. Allogeneic transfusions were found to decrease macrophage migration in response to inflammatory stimuli and to increase their production of the strongly immunosuppressive arachidonic acid metabolite prostaglandin E. Syngeneic transfusions did not alter macrophage migration or arachidonic acid metabolism. The immunosuppression seen following transfusions appears to be related to an increased synthesis of prostaglandin E.

Animals↗

Effect of transfusion on immune function in a traumatized animal model. II. Effect on mortality rate following septic challenge.

It is well established that transfusions given prior to transplantation diminish rejection, and recent reports suggest that transfused patients having surgery for cancer developed more metastases than those who did not receive transfusions. To our knowledge, however, there are no studies evaluating whether transfusions result in increased rates of infections. To investigate this, 295 Lewis rats were subjected to a 25% total body surface area burn and were given either 3 mL of Lewis blood, 3 mL of A'Solagoft Cancer Institute rat blood, or 9 mL of lactated Ringers' solution intravenously on day 1 before burn or on the day of burn. One additional group received 1-mL transfusions on days 9, 7, and 5 before burn. The burns were painted with 1 X 10(8) Pseudomonas aeruginosa lot No. 1244 on postburn days 0, 1, or 2. All rats were followed up for 28 days and survival and mean survival times were recorded. Transfusion of A'Solagoft Cancer Institute blood increased mortality unless given within 24 hours prior to Pseudomonas challenge, when it diminished mortality. Transfusion with syngenic Lewis blood had no effect. We conclude that transfusions may adversely affect survival when given before bacterial challenge, possibly due to immunosuppression from exposure to non-self-histocompatibility antigens.

Animals↗

Effect of blood transfusion and anesthesia on resistance to bacterial peritonitis.

Patients who undergo gastrointestinal operations and require prolonged anesthesia or blood transfusions have been reported to have a higher incidence of infectious complications. A rat peritonitis model was used to determine if the increased rate of infection was due to the severity of their underlying disease process or to possible immunosuppressive effects of transfusions and anesthesia. Four hundred adult Lewis rats were divided into four groups. Each group received either 0.5 ml of allogenic blood, 0.5 ml of syngeneic blood, metaphane anesthesia, or 1.5 ml of saline. They were challenged with either 1 X 10(8) or 1 X 10(7) Escherichia coli on the day of transfusion or 4 days after transfusion. Survival rates and mean survival times were determined. Syngeneic transfusions were found not to significantly impair survival. Anesthesia administration resulted in a moderate impairment in survival. Allogeneic blood transfusions caused the most severe impairment with a greater than 50% decrease in survival rates compared to controls in three of the four groups tested. Blood transfusions would thus appear to impair resistance to bacterial infections to an even greater degree than anesthesia. Unnecessary transfusions should therefore be avoided.

Anesthesia, General↗