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Biomedical subjects

J P Waymack

Publications and source records attributed to J P Waymack.

At least 73 records · Page 4Linked to original sources

The effect of donor specific transfusions and dietary fatty acids on rat cardiac allograft survival.

A rat heterotopic cardiac transplant model was used to study the effect of dietary lipids on the immune response. Animals receiving linoleic acid (LA), oleic acid (OA), and fish oil (FO) enriched diets showed significant prolongation of allograft survival when compared to the control diet fed animals. When LA was given to animals who had received a single donor specific transfusion (DST) augmentation of the beneficial DST effect was observed, while the OA and FO fed groups showed no differences from control DST animals. Dietary regulation of the immune response, possibly through manipulation of arachidonic acid metabolism, is implied.

Animals↗

Lack of effect of enteral antibiotics on the post-burn hypermetabolic response.

Burn patients who survive the initial 24 h following major burn injury commonly develop a marked hypermetabolism. One of the possible mechanisms of this increased metabolic rate is gut translocation of bacteria and endotoxin following burn injury. We attempted to decrease the hypermetabolism by administering various antibiotic and endotoxin binding agents enterally in a burned guinea-pig model. Adult guinea-pigs were given polymyxin B, trimethoprim and sulphamethoxazole, or neomycin and clindamycin, or Kaopectate, sodium deoxycholate, neomycin, clindamycin and polymyxin B. A control group received no drugs. The drugs were administered through a gastrostomy tube beginning the day before burn injury and continuing for 14 days. There was no significant decrease in the resting metabolic rate in any of the treated groups compared to controls. Neither enteral antibiotics nor endotoxin binding agents were able to induce a significant reduction in the post-burn hypermetabolic response in this model.

Animals↗

Renal calculi in the burned child.

Fifteen burned children were noted to have developed renal calculi at our institution over the past 20 years. Primary risk factors appear to be immobilization and a high intake of dairy products and antacids. Presenting symptoms and physical signs include abdominal pain, haematuria, with transient leukocytosis and elevations of the blood urea nitrogen. Conservative therapy with increased fluid administration and urine acidification were successful in 13 of the patients. The remaining two patients required surgical extraction. There were no long-term renal sequelae in any of the patients.

Adolescent↗

Hematuria in the burned child.

Hematuria is a frequent complication in burn patients, but its clinical significance has not been reported. The incidence, etiologies, treatment, and outcome of hematuria in 1,785 burn patients treated from 1964 to 1983, have been reviewed. Ninety-one patients had hematuria (greater than 15 RBC/HPF with unspun urine). There were five main causes: urinary infections (UTI), 50 cases; renal calculi (RC), 14 cases, including 3% and 5% total body surface area burn patients; catheter trauma, 7 cases; renal vein thrombosis (RVT), 5 cases; and acute renal failure (ATN), 4 cases. Ten patients died in the UTI group, five with Candida as the infecting organism. No RC patients died, but two required surgical extraction of their stones. This incidence of RC may be due to large intake of dairy products and antacids and to prolonged immobilization. The catheter trauma group had no deaths and was the youngest group. One RVT patient was diagnosed clinically and successfully treated surgically. The other three were diagnosed at necropsy. The ATN patients all developed renal failure late as part of multiple organ system failure and all died. We conclude hematuria is a serious finding in burn patients and prompt diagnosis of its etiology and treatment are essential for maintaining renal function and patient survival.

Acute Kidney Injury↗

A prospective study of thymopentin in severely burned patients.

A randomized prospective double-blind study of thymopentin was performed upon 24 severely burned patients to evaluate its efficacy in correcting postburn immunologic abnormalities and preventing infectious morbidity and mortality. Patients in the treated group received 50 milligrams of thymopentin daily for the first two weeks after injury and three times weekly thereafter until the patient was no longer at risk for having infections develop. The placebo group received saline solution intravenously. The rate of infectious complications was recorded. Immunologic tests used at least weekly were: white blood cell counts, OKT4 to OKT8 ratios, lymphocyte blastogenesis and neutrophil bactericidal index. There were no differences noted in patient mortality, infectious complications or antibiotic use. There were two significant differences noted among the immunologic tests. First, there was a decreased lymphocyte blastogenic response in the treated group at two weeks after injury without a difference in T4 to T8 ratios. Second, there was less leukopenia during the first week after injury in the treated group.

Adolescent↗

Effect of transfusion on immune function in a traumatized animal model.

Blood transfusions repeatedly have been shown to prolong allograft survival, probably by stimulating suppressor T lymphocytes. The effects of transfusions on immune function in traumatized patients has not previously been investigated. We investigated the effects of transfusions on the immune system using a burned rat model. The transfusions were found to have no effect on the white blood cell counts, differential cell count, or neutrophil migration and bactericidal index. Those animals that received transfusion did exhibit impaired cell-mediated immunity and macrophage migration. Blood transfusions seem to increase further the immunosuppression seen with trauma and surgery.

Animals↗

Blood transfusions as an immunomodulator--a review.

Blood transfusions have been shown for two decades to prolong allograft survival. The mechanism is complex, involving both T lymphocytes and macrophages. In the last five years, transfusion induced immunosuppression has been shown to increase the rate of tumor growth and to increase susceptibility to infectious complications. Prevention of this immunosuppression may be possible by the concomitant use of immunomodulators which inhibit suppressor T lymphocyte function or block prostaglandin E production. A second potential but as yet unproven method is by use of frozen washed red blood cells when transfusions are required.

Adjuvants, Immunologic↗

Immunostimulation by TP-5 in immunocompromised patients and animals--current status of investigation.

TP-5 is a pentapeptide containing active site of the thymic hormone, thymopoietin. It has been shown to exert effects on multiple components of human and animal immune system both in vivo and in vitro. Initial studies demonstrated it to be necessary for T lymphocyte maturation. Its effects on other parts of the immune system are primarily immunostimulatory, and the drug can be used to correct immunodeficiencies resulting from several causes. TP-5 has been shown to improve survival rates in multiple animal studies where the animal has been rendered immunodeficient prior to septic challenge. It has also been successful in preventing and treating infections in a number of human studies. Evaluation of the exact mechanism by which the drug improves survival has demonstrated that it is of complex nature, involving interactions between various types of white blood cells.

Adjuvants, Immunologic↗

Release of burn scar contractures of the neck in paediatric patients.

Burn scar contractures of the neck represent a continuing problem for plastic surgeons. A review of 143 neck-release procedures performed at the Cincinnati Shriners Burns Institute documented a high rate of contracture recurrence. This was especially true in those patients who had previously suffered burns to the entire anterior neck. Treatment of this condition with Z-plasties, or releasing incisions with split thickness skin grafts, had a recurrence rate of 81 per cent and 62 per cent, respectively. The use of a neck hyper-extension brace for over 1 year following skin grafting decreased the recurrence rate to 17 per cent. In patients who were not compliant in wearing a brace, the best result was obtained by using a full thickness skin graft in the release site. Contractures resulting from smaller burns were successfully handled by a variety of techniques.

Braces↗

An evaluation of Aquaphor Gauze dressing in burned children.

Aquaphor Gauze was evaluated as a dressing for skin graft donor sites, for partial thickness burn injuries and for split thickness skin grafts. Control dressings consisted of: fine mesh gauze for skin graft donor sites. silver sulphadiazine (Silvadene) on coarse mesh gauze for the partial thickness burns, and nitrofurazone cream (Furacin) on fine mesh gauze for the skin grafts. The Aquaphor Gauze was found to be inferior to the fine mesh gauze for donor site dressings. No statistically significant difference was identified between Aquaphor Gauze and controls for the treatment of partial thickness burns. As a dressing for skin grafts the Aquaphor Gauze was significantly superior to the control dressing as measured by graft take and reduced patient pain. We would recommend that Aquaphor Gauze be used as a dressing for skin grafts where the risk of infection is not excessive.

Adolescent↗

Effect of Dazmegrel (UK-38,485) on immune function in a burned guinea-pig model.

We investigated the effects of Dazmegrel, a highly effective and selective thromboxane synthetase inhibitor, on the immune system in a bilateral 5 per cent total body surface area (TBSA) deep partial thickness scald in a guinea-pig model. The animals were randomized into two groups: one received Dazmegrel at 3.4 mg kg-1 day-1 by i.m. injection; the other received the same volume of saline. Cell-mediated immunity was evaluated by the response to the hapten dinitrofluorobenzene (DNFB), as measured by ear swelling in response to cutaneous application. The ear swelling of the Dazmegrel-treated group was 52.8 +/- 3.8 per cent, compared to 41.4 +/- 2.4 per cent for the control group (P less than 0.02). Neutrophil bactericidal function was determined on post-burn day (PBD) 7 and opsonic function on both post-burns days 7 and 22. The serum opsonic indices were nearly identical at both times, but the Dazmegrel-treated animals had a significantly improved neutrophil bactericidal index (1.15 +/- 0.05 v. 1.68 +/- 0.17, P less than 0.01). Dazmegrel exerted a stimulating effect on the immune system in this burn model, improving neutrophil antibacterial function and cell-mediated immunity.

Animals↗

The effect of the thromboxane synthetase inhibitor Dazmegrel (UK-38,485) on wound healing, dermal ink perfusion and skin blood flow measurements in deep partial thickness burns.

A guinea-pig model was used to evaluate the effect of Dazmegrel (UK-38,485), a new highly selective inhibitor of thromboxane synthetase, on burn wound healing. Dazmegrel had a beneficial effect on wound healing when given systemically at a dosage of 3.4 mg kg-1 day-1 but higher doses had no effect. There was no change in dermal perfusion measured by India ink injection or by 133Xe injection in any of the groups receiving parenteral Dazmegrel. Neither was the number of hair follicles in the healing burn wound significantly different between the treated and control animals. When Dazmegrel was applied topically, it inhibited wound healing. These findings are consistent with previous reports from different laboratories that prostaglandin inhibitors impair healing of the burn wound when applied topically but improve wound healing when given parenterally. The present study further suggested that the improvement in wound healing in this model was not mediated by improved dermal perfusion.

Administration, Topical↗

Effect of blood transfusions on macrophage-lymphocyte interaction in an animal model.

Blood transfusions have been reported over the last 2 decades to decrease allograft rejection, to increase the rate of tumor growth, and to increase susceptibility to infectious complications. The effect of transfusions on macrophages, specifically on their regulation of lymphocyte proliferation, was investigated. Both macrophages and their supernatants obtained from transfused rats impaired lymphocyte blastogenesis to a greater degree than those from nontransfused rats. This effect was greatest when the lymphocytes were subjected to mitogen stimulation. The immunosuppression was seen with macrophages from both allogeneically and syngeneically transfused rats. Blood transfusions exert their immunosuppressive effect at least in part by increasing macrophage suppression of lymphocyte response to stimuli.

Animals↗

Mechanisms of action of two new immunomodulators.

Despite antibiotics, infection remains a significant problem in surgical patients. The reasons are multiple, and include acquired immunologic deficiencies that are seen in malnutrition, sepsis, trauma, and burns. Two immunomodulators, thymopentin (TP-5) and CP-46,665, have been shown to improve survival in infectious animal models of such deficiencies. We investigated the mechanism of action in guinea pigs subjected to a burn of 30% of the total body surface area. These animals received 0.3 mg/kg of thymopentin, 0.3 mg/kg of CP-46,665, or saline solution. Neutrophils, macrophages, and serum samples were obtained from the animals and tested for their ability to phagocytose and kill Pseudomonas aeruginosa. The serum was tested for its ability to opsonize Escherichia coli. Thymopentin was found to improve neutrophil function on postburn days 2 and 4 and to improve macrophage function on postburn day 4. CP-46,665 was found to improve both macrophage function and opsonization on postburn day 2.

Adjuvants, Immunologic↗

Acute upper airway obstruction in the postburn period.

Upper airway obstruction in the severely burned patient is a well-known problem that is due to mucosal edema secondary to the effects of toxic substances and heat on the laryngeal and tracheal mucosa. Herein, we report a different cause of airway obstruction seen in the late postburn period during the induction of anesthesia for reconstructive procedures. This obstruction is due to the presence of severe burn-scar contractures of the neck that prevent successful endotracheal intubation. We have seen this occur 17 times in 13 patients. All of the patients were successfully treated by an emergency neck release, after which most of the patients could be intubated and the release then skin grafted. Surgeons operating on patients with scar contractures of the neck should be aware of this condition and its appropriate treatment.

Adolescent↗

Early vascular grafting to prevent upper extremity necrosis after electrical burns. Commentary on indications for surgery.

Early vascular grafting is the only effective form of treatment for electrical burns of the wrist which are severe enough to impair blood flow to the hand. Failure to appreciate the significance of early changes in blood flow and to take prompt appropriate action may result in the irreversible loss of blood supply and subsequent amputation. This report analyses the problems encountered in six patients where the early signs of impaired blood flow were not appreciated and amputations were subsequently required.

Adult↗

Immunomodulators in the treatment of peritonitis in burned and malnourished animals.

Deficiencies in the immune system that lead to increased morbidity and mortality from infectious complications have been well documented in patients suffering from trauma, malnutrition, sepsis, and thermal injuries. We investigated the potential benefit of immune stimulation for preventing infection in such conditions in an animal model by evaluating three drugs: Corynebacterium parvum, thymopentin (TP-5), and CP-46,665. One-hundred eighty female guinea pigs were rendered immunodeficient by first inflicting a 30% total body surface burn and then placing the animals on diets with calories inadequate to maintain body weight. One half of the animals were then given one of the three immunomodulators on the first, third, and fifth days after burn injury, to try to reverse immunodeficiency. The remaining animals received saline solution injections. Animal responses were evaluated by inserting a clot containing Escherichia coli and Bacillus fragilis into their peritoneal cavity 6 days after burn injury. The animals were followed for 21 days after burn injury. Autopsies on those that died revealed peritonitis and/or pneumonia; autopsies on these that survived showed no pneumonia and there was consistent resolution of peritonitis. TP-5 and CP-46,665, but not C. parvum, significantly improved survival rates and mean survival time in those animals receiving 100 kcal/kg/day. TP-5 and CP-46,665 may be of benefit to the severely stressed, malnourished surgical patient who is at risk of bacterial infection.

Adjuvants, Immunologic↗