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J P Waymack

Publications and source records attributed to J P Waymack.

At least 37 records · Page 2Linked to original sources

A comparison of triple-therapy with double-therapy immunosuppression in cadaveric renal transplantation.

Triple-therapy (low-dose cyclosporine-azathioprine-prednisone) immunosuppression regimen was compared with double-therapy (cyclosporine-prednisone) in 91 consecutive nonrandomized adult cadaveric renal transplant recipients. Both groups were comparable with respect to ethnic diversity, prior transplants, and diabetes. The majority of patients with delayed function (ATN) were maintained on triple therapy, and the use of antilymphocyte agents was more common in the triple-therapy group (52% vs. 7%; P = 0.0001). Triple-therapy patients experienced increased acute rejection episodes (1.4 vs. 0.8 per patient, P = 0.03), required more courses of additional steroid pulse therapy (4.3 vs. 1.6 per patient; P = 0.001), and developed serious infections more frequently (37% vs. 15%; P = 0.05), especially CMV infections (17% vs. 0; P = 0.03), compared with double-therapy patients. However, the increased overall infection rate and CMV infection rate were observed only in those patients who received antilymphocyte agents compared with those who did not (46% vs. 21%; P = 0.02 for all infections, 26% vs. 4%; P = 0.006 for CMV). Additional steroid pulse therapy was associated with increased CMV infections (24% vs. 0; P = 0.03) but not with overall infections. One-year allograft and patient survival were equivalent in both groups. Exclusion of ATN patients from analysis did not alter the findings. This experience confirms the overall efficacy of triple-therapy immunosuppression in renal transplant recipients but suggests that triple therapy may be associated with more acute rejection episodes, greater immunosuppression requirements, and a resultant increase in infections, especially CMV.

Adolescent↗

Effect of prostaglandin E on immune function in normal healthy volunteers.

Prostaglandin E (PGE) has been hypothesized to be the endogenous metabolite that results in the immunosuppression seen in patients with tumor and trauma. This has resulted in multiple investigators proposing that administration of PGE inhibitors, such as aspirin and indomethacin, might improve immune function in such patients. We administered a long acting PGE analog, misoprostol, to nine normal healthy volunteers for five days and assayed immune function before and after therapy. The PGE analog improved lymphocyte blastogenesis and increased tumor necrosis factor production. The PGE analog also resulted in the volunteers having symptoms similar to those seen in patients with sepsis. The results of these studies indicate that elevated levels of PGE do not seem to result in impairment of immune function, but may be the endogenous metabolite responsible for the symptologic factors seen in infected patients.

Adult↗

The effect of erythropoietin in normal healthy volunteers and pediatric patients with burn injuries.

BACKGROUND: Surgical procedures result in blood loss that can require replacement transfusions. Such therapy may result in multiple adverse sequelae, including transmission of infectious diseases and immune impairment. Alternative therapies are therefore desirable. METHODS: We evaluated the ability of recombinant human erythropoietin (rEPO) to increase red blood cell production in both normal healthy volunteers and patients with burn injuries. The effect of rEPO on immune function in the volunteers was also evaluated. The volunteers received 150 units/kg rEPO daily for 7 days, with immune function and hematopoiesis assayed on days 0, 7, and 14. The patients with burn injuries received either 500 units/kg/day rEPO with iron supplementation or merely the iron. RESULTS: rEPO increased erythropoiesis in both the volunteers and the patients with burn injuries. Failure to provide iron supplementation to the volunteers resulted in significant depletion of iron stores with a concomitant impairment in immune function that paralleled the iron depletion. CONCLUSIONS: rEPO therapy offers the potential to increase red blood cell production in surgical patients. Failure to provide iron supplementation in patients receiving rEPO can lead to a rapid depletion of iron stores and may contribute to an immune dysfunction.

Adult↗

Alterations in host defense associated with anesthesia and blood transfusions. II. Effect on response to endotoxin.

The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.

Anesthesia, General↗

Effect of prostaglandin E in multiple experimental models. VIII. Effect on host response to metastatic tumor.

Prostaglandin E (PGE) is produced by certain tumors and is reported to decrease primary tumor growth. We evaluated its effect in multiple tumor models utilizing a 1 week course of the long acting PGE derivative dimethyl-PGE (dPGE) at a dosage of 100 micrograms/kg/day vs. a lactated Ringers control. For all tumor models, a suspension of 1 x 10(6) colon carcinoma cells were injected into Wistar-Furth rats. When the suspension was injected subcutaneously and the drug was begun at the time of tumor challenge, there was no effect on survival. When the tumor was injected intraperitoneally or intravenously and the drug begun at the time of tumor challenge, dPGE decreased survival time. When the tumor was administered intravenously but dPGE was delayed for 5 days, there was no effect on survival time. When rats were given a 1 week course of dPGE or saline, dPGE was found not to alter natural killer (NK) cell cytotoxicity, macrophage cytotoxicity, spontaneous lymphocyte blastogenesis, or mitogen stimulated blastogenesis. dPGE failed to alter lymphocyte metabolism of glucose in nonstimulated lymphocytes, but decreased the rate of glucose metabolism and adenosine deaminase activity in mitogen stimulated lymphocytes. In conclusion, PGE appears to enhance metastatic growth of tumor lines where it does not alter primary tumor growth. This effect does not appear immunologically mediated.

Animals↗

Effect of prostaglandin E in multiple experimental models: V. Effect on tumor/host interaction.

Prostaglandin E (PGE) has long been incriminated as a cause of the immunosuppression seen in cancer patients and for the increased rates of tumor growth due to the impairment of the immunologic response to the tumor. We have investigated the effect of PGE on tumor-host interaction by utilizing a parenterally administered long-acting PGE derivative, 16,16-dimethyl-prostaglandin E (dPGE). Administration of dPGE was found to decrease the rate of tumor growth but at a cost of decreasing tumor-free body mass. The dPGE did not alter resting metabolic rates but did alter some parts of brain dopamine metabolism and significantly decreased the serum level of multiple amino acids. In conclusion, elevated PGE levels may significantly alter metabolism in tumor patients.

Amino Acids↗

Effect of prostaglandin E in multiple experimental models. IV. Effect on resistance to endotoxin and tumor necrosis factor shock.

Administration of a long-acting prostaglandin E, 16,16-dimethyl-PGE (dPGE), to rats improves their survival of bacterial peritonitis. We examined the mechanism of this protective effect with reference to its interaction with the release of cachectin (TNF). Sixty rats received saline, 20 micrograms/kg dPGE, or 80 micrograms/kg dPGE 12 hr prior to endotoxin and continuing for 48 hr. Survival rates for the saline, 20 micrograms/kg dPGE, and 80 micrograms/kg dPGE groups were 0, 40, and 85%, respectively. Forty rats received saline or 80 micrograms/kg dPGE, with the initial dose being 3 hr following endotoxin challenge and continuing for 48 hr. Survival rates for both groups were 0%. Sixty rats received saline or 80 micrograms/kg dPGE at 12 and 1 hr prior to endotoxin. Two hours after challenge, they were sacrificed and plasma TNF levels were assayed. The plasma TNF level in saline-treated rats was 22.72 +/- 0.83 ng/ml and in the dPGE-treated group, 16.03 +/- 1.13 ng/ml (P less than 0.001).

Animals↗

The effect of blood transfusions on immune function. V. The effect on the inflammatory response to bacterial infections.

Blood transfusions have been shown to be associated with increased bacterial infection rates in colon cancer patients and in multiple animal studies. This increased susceptibility appears due to impairments in the systemic resistance to infections and not to alterations in the local response. Specifically, transfusions in a rat model were not found to alter the peritoneal cavity's response to an Escherichia coli challenge or the burn wound's response to a Pseudomonas aeruginosa challenge. Transfusions did impair the macrophage's ability to phagocytose and kill bacteria. Transfusions also increased the serum level of the immunosuppressive glucocorticoid, corticosterone.

Analysis of Variance↗

Bashkirian train-gas pipeline disaster: the American military response.

The United States Army Institute of Surgical Research was asked to provide burn care assistance in June 1989 following the explosion of leaking methane/propane gas in the Central Soviet Union, which destroyed two passenger trains and injured 800 passengers. A 17-member burn team flew from San Antonio, Texas, to Ufa, USSR and assisted in the management of 150 burn patients in a general medical-surgical hospital. Early problems included heavily colonized burn wounds, with a microbial flora that demonstrated broad antibiotic resistance. As wound complications were controlled, 28 operative procedures were performed to excise and graft the burn wounds. The recommendations for burn disaster management, based on our experience in Ufa, should be of assistance to other groups that may be asked to provide similar assistance in the future.

Bashkiria↗

Bashkiria train-gas pipeline disaster: a history of the joint USSR/USA collaboration.

In June 1989, a methane/propane pipeline explosion destroyed two passenger trains in the Bashkirian Republic of the Soviet Union. Over 400 passengers died immediately and 806 were injured. Most of those injured suffered thermal injuries. One hundred and fifty patients were treated at Hospital 21 in Ufa, Bashkiria, by a combined Soviet-US team. Twenty-six patients underwent excision and grafting of their burn wounds. Microbiological studies indicated significant resistance to locally available antibiotics. Antibiotics provided by the US team proved useful in treating the resistant organisms. This disaster and the international response to it exemplify the need for a coordinated response to major burn disasters and the positive results of international cooperation.

Bashkiria↗

Effect of prostaglandin E in multiple experimental models. VII. Effect on resistance to sepsis.

The immunosuppression seen following burn injury has frequently been attributed to elevated prostaglandin E levels. We evaluated the contribution of elevated prostaglandin E levels on susceptibility to infectious complications utilizing multiple mouse models. The administration of 100 micrograms/kg of the long-acting derivative of prostaglandin E, 16,16-dimethyl-prostaglandin E, was found to improve survival in C3/HEN mice challenged with 1 x 10(8) Escherichia coli organisms intraperitoneally. The administration of indomethacin was found to decrease survival in the same model. With C3/HEJ (endotoxin-resistant) mice, indomethacin was found to increase mortality rates in animals challenged with 1 x 10(8), 1 x 10(9) or 1 x 10(10) Escherichia coli organisms. These findings suggest that elevated prostaglandin E levels seen in burn patients may not be responsible for the postburn increased susceptibility to infectious complications.

Animals↗

Pathogenicity of the enterococcus in surgical infections.

The enterococcus has been relegated to a position of unimportance in the pathogenesis of surgical infections. However the increasing prevalence and virulence of these bacteria prompt reconsideration of this view, particularly because the surgical patient has become increasingly vulnerable to infectious morbidity due to debility, immunosuppression, and therapy with increasingly potent antibiotics. The enterococcus is a versatile opportunistic nosocomial pathogen, causing such diverse infections as wound, intra-abdominal, and urinary tract infections; catheter-associated infection; suppurative thrombophlebitis; endocarditis; and pneumonia. Although surgical drainage remains the cornerstone of therapy for enterococcal infections involving a discrete focus, in the circumstances typified by the compromised surgical patient, specific antibacterial therapy directed against the enterococcus is warranted. Recent evidence indicates that parenteral antibiotic therapy for enterococcal bacteremia is mandatory and that appropriate therapy clearly reduces the number of deaths.

Cross Infection↗

The effect of transfusions on the incidence of bacterial infection.

The use of blood transfusions has been a art of medical practice for over half a century. The efficacy of blood and blood products in patients in hypovolemic shock from trauma or operative procedures has been well established. During the past quarter century, it has been demonstrated that blood transfusions administered prior to transplantation decrease the frequency and severity of allograft rejection. More recent work has indicated that this beneficial effect is the result of the transfusion inducing a state of immunosuppression in the recipient. A number of reports have suggested that this posttransfusion immunosuppression may result in an increased susceptibility to bacterial infections.

Animals↗

Antibiotics and the postburn hypermetabolic response.

Severe burn injury has been documented to significantly increase resting metabolic energy expenditure. This increase in metabolic rate appears to be possibly correlated with the degree of burn wound colonization and infection with bacteria. Prevention of such colonization and infection through the use of topical antimicrobial agents appears to decrease the metabolic alterations resulting from burn injury. These findings indicate that appropriate use of topical antibacterial agents may decrease the metabolic demands seen in burned patients. Burn-induced translocation of intestinal bacteria has also been hypothesized to contribute to the postburn hypermetabolic response. Attempts at preventing this entity in a burned guinea pig model through the use of selective decontamination of the digestive tract by the administration of enteral antibiotics have failed to demonstrate any measurable effect.

Animals↗

Effect of blood transfusions on immune function. Part VI. Effect on immunologic response to tumor.

Transfusions are reported to increase the incidence of tumor metastasis in clinical studies and primary tumor growth in animal studies. We evaluated the effect of transfusions on immunologic response to primary and metastatic tumors in multiple rat models. One half of the animals were administered lactated Ringer's solution and one half ACI rat blood at the time of tumor challenge. In 80 rats a slow-growing colon tumor was implanted subcutaneously. At 4 months there were no significant differences in tumor size or leukocyte infiltration of the tumor. Similar results were obtained with a rapidly growing colon cancer. Analysis of T-lymphocyte subpopulations in both groups showed no differences. Rats transfused at the time of intravenous challenge with a suspension of 1 x 10(6) tumor cells had a mean survival time of 38.3 +/- 0.8 days and the control group had a mean survival time of 41.1 +/- 0.8 days (p = 0.016). One week after transfusion, natural killer cell lysis of tumor cells at a 100:1 effector/target cell ratio was 18.0% +/- 1.8% in the transfusion group and 23.0% +/- 1.3% in the control group (p = 0.034). In conclusion, transfusions in multiple rat cancer models did not affect primary tumor growth or the host's immunologic response to it but did significantly impair natural killer cell function and survival with tumor metastases.

Adenocarcinoma↗

Burn wound care.

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Burns↗