Biomedical subjects

J P Waymack

Publications and source records attributed to J P Waymack.

At least 19 recordsLinked to original sources

PubMed1997

Academic surgeons' knowledge of Food and Drug Administration regulations for clinical trials.

OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels. DESIGN: Survey of surgical department faculty members in 20 universities. RESULTS: Sixty-five responses were received from 14 sites. Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The best predictor of overall score was being a primary investigator of a clinical trial (P < .001), followed by being or having been a member of an IRB (P < or = .02). The total mean score of members of the Surgical Infection Society (8.2 +/- 0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a phenomenon not observed with other surgical societies. In certain hypothetical clinical scenarios, all respondents were mistakenly willing to conduct clinical trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB member respondents and 16 (25%) of the 65 respondents were willing to conduct human research without appropriate approval from patients, the IRB, or both. CONCLUSIONS: Knowledge deficits exist in the academic surgical community about the role and requirements of the FDA and local IRBs for conducting clinical research. Further study is required to determine the reasons for this deficit and to identify appropriate interventions.

Clinical Trials as Topic↗

PubMed1996

Trauma, shock, and gut translocation.

This article reviews the scientific and clinical evidence that supports trauma and shock as potential etiologies for translocation of intestinal microorganisms and their by-products. The potential for loss of intestinal barrier function to cause the eventual septic deaths observed in such patients, as well as possible mechanisms for preventing and treating this entity is also discussed.

Animals↗

PubMed1995

A double-blinded prospective evaluation of recombinant human erythropoietin in acutely burned patients.

OBJECTIVE: To evaluate the effects of recombinant human erythropoietin (r-HuEPO) in attempting to prevent anemia in acutely burned patients. DESIGN: Prospective double-blind randomized study of 40 patients. METHODS: Patients with burns from 25% to 65% total body surface were enrolled. r-HuEPO or a placebo was begun within 72 hours of admission. Cell blood count, reticulocyte counts, transfusion requirements, and blood loss were measured. Comparison was carried out by the unpaired t test. MAIN RESULTS: There was no statistically significant difference in hemoglobin, hematocrit, reticulocyte count, ferritin, serum iron, total iron blinding capacity, or transfusion requirements. In patients with burns from 25% to 35%, the reticulocyte counts were statistically significantly higher. CONCLUSION: In our work the administration of r-HuEPO in acutely burned patients did not prevent the development of postburn anemia or decrease transfusion requirements. Increased erythropoiesis in smaller burns (25% to 35%) was observed and may indicate a reason for further study.

Adolescent↗

PubMed1994

Recent advances in burn care.

Over the past few decades, the mortality related to thermal injuries has been significantly reduced. This has been accomplished through an increased understanding and subsequent management of inhalation injury, the postburn hypermetabolic response, and immunocompromise. In addition, the prompt excision of the burn wound and early permanent closure has decreased the length of hospital stay and has facilitated timely social reintegration of the burned patient.

Burns↗

PubMed1994

Effect of PGE in multiple experimental models. IX: In vivo effects of PGE on immune response of leucocytes to wounds.

There have been conflicting results obtained when comparing the in vitro with in vivo effects of prostaglandin E (PGE) on immune function. The in vitro studies have demonstrated immune suppression with PGE administration while the in vivo studies demonstrated improved survival when utilizing infected models. To attempt to resolve this discrepancy, we evaluated the in vivo effect of PGE on host immune function utilizing multiple rat models. PGE was found to have no effect on the ability of leucocytes to infiltrate a sponge matrix wound over a 2-week period of study. PGE also failed to alter the percentage of T-lymphocyte subset populations infiltrating the sponge matrix model. There was noted to be no effect of PGE on the ability of neutrophils to chemiluminescence, or on metabolic function of lymphocytes. In conclusion, PGE does not appear to have immunosuppressive properties when studied using certain in vivo models.

Amino Acids↗

PubMed1993

Surgical Infection Society intra-abdominal infection study. Prospective evaluation of management techniques and outcome.

This prospective, open, consecutive, nonrandomized trial examined management techniques and outcome in severe peritonitis. A total of 239 patients with surgical infection in the abdomen and an APACHE (acute physiology and chronic health evaluation) II score greater than 10 were studied. Seventy-seven patients (32%) died. Reoperation had a 42% mortality rate (35 of 83 patients died) compared with a 27% mortality rate (42 of 156 died) in patients who did not undergo reoperation. Forty-six patients underwent one reoperation; 15, two reoperations; 10, three reoperations; five, four reoperations; and seven, five reoperations, with mortality rates of 43%, 40%, 30%, 40%, and 57%, respectively. There was no significant difference in mortality between patients treated with a "closed-abdomen technique" (31% mortality) and those treated with variations of the "open-abdomen" technique (44% mortality). Logistic regression analysis showed that a high APACHE II score, low serum albumin level, and high New York Heart Association cardiac function status were significantly and independently associated with death. Low serum albumin level, youth, and high APACHE II score were significantly and independently associated with reoperation.

Abdomen↗

PubMed1993

Impact of exogenous insulinlike growth factor 1 on hepatic energy metabolism in burn injury.

BACKGROUND: Insulinlike growth factor 1 (IGF-1) has previously been demonstrated to improve the nutritional status of burned animals. The method by which it achieves this result has not yet been fully elucidated, but may be the result of alterations in hepatic metabolism. OBJECTIVE: To determine if IGF-1 is able to correct the burn-induced impairments in hepatic metabolic function. DESIGN: Seventy-two Sprague-Dawley rats were subjected to a sham burn (n = 24), or a 50% total body surface area scald burn (n = 48). Half the scald burn group received 3 micrograms/kg per day of IGF-1. The remainder received a placebo. The rats were sequentially assayed for multiple components of hepatic function. RESULTS: Insulinlike growth factor 1 corrected the burn-induced decrease in hepatic adenosine triphosphate concentration and prevented the burn-induced increase in hepatic ketone body levels. Insulinlike growth factor 1 was also able to prevent the burn-induced decrease in the hepatic acetoacetate-beta-hydroxybutyrate ratio. Since this ratio is directly proportional to mitochondrial redox potential this indicates that IGF-1 is also able to prevent the burn-induced impairment in hepatic redox potential. CONCLUSIONS: These data indicate that part of the previously demonstrated beneficial effect of IGF-1 in burn injury may be due to its ability to improve multiple components of hepatic metabolism.

Adenosine Triphosphate↗

PubMed1993

Effect of insulin-like growth factor 1 on host response to tumor.

Oncology patients suffer multiple detrimental metabolic alterations. Among these are catabolism of tumor free body mass to supply nutrients to feed the tumor. This results not only in enhanced tumor growth but also poor wound healing and immunosuppression of the tumor host. Efforts are therefore being directed at finding methods for improving the nutritional status of the tumor host without enhancing tumor growth. We investigated the ability of two hormones, insulin-like growth factor-1 (IGF-1) and insulin, to improve physiologic function in tumor-bearing animals. Tumor-bearing animals received a continuous infusion of IGF-1 (2.20 mg/kg/day), insulin (820 microns/kg/day) or placebo via an osmotic minipump for 7 days. All animals were pair fed to eliminate nutritional intake as a variable. The placebo group lost 31.37 +/- 4.3 g of tumor free body mass during the study period. The insulin treated group lost 26.34 +/- 7.42 g and the IGF-1 group lost 5.07 +/- 3.25 g (P < 0.001, ANOVA). IGF-1 treatment failed to alter plasma glucose, lactate, or total amino acid concentration and failed to alter hepatic ketone body concentrations, but did improve hepatic mitochondria redox potential. Finally, IGF-1 improved splenic weight by 110% and splenic lymphocyte count by 300%. In conclusion IGF-1 appears to offer potential in supporting tumor free host body mass without stimulating tumor growth.

Amino Acids↗

PubMed1993

Blockade of prostaglandin products augments macrophage and neutrophil tumor necrosis factor synthesis in burn injury.

Cyclooxygenase products are believed to be a major regulator of host tumor necrosis factor-alpha (TNF-alpha) production in response to trauma and sepsis. To study this relationship, Lewis rats underwent a 30% burn or sham burn. Dimethyl-prostaglandin E (dPGE, 50 micrograms/kg), ibuprofen (IFU, 2 mg/kg), or saline was administered twice daily. Rats were sacrificed at Day 7 to obtain Kupffer cells, peritoneal macrophages, splenic macrophages, and neutrophils. For in vivo studies, 10(6) cells from each group were cultured with 10 micrograms of lipopolysaccharide (LPS). For in vitro studies, cells from the burn and sham groups were cultured with LPS and dPGE (10 micrograms/ml), IBU (10 micrograms/ml), or saline. The supernatants were harvested after 2, 6, and 24 hr of culture and assayed for TNF-alpha (mu/ml) by L929 cytolysis. Burn injury resulted in a significant increase in Kupffer cell and neutrophil TNF-alpha production compared to the sham group (P < 0.001, ANOVA). The administration of IBU to burned animals led to a pronounced elevation of TNF-alpha production by Kupffer cells, peritoneal macrophages, and neutrophils compared to vehicle-treated burned animals (P < 0.001, ANOVA). With in vitro studies, IBU increased Kupffer cell, peritoneal macrophage, and neutrophil TNF-alpha release by 213, 327, and 198%, respectively (P < 0.05, ANOVA). dPGE caused a marked decrease in Kupffer cell and peritoneal macrophage TNF-alpha synthesis by 50 and 43%, respectively (P < 0.01, ANOVA). In conclusion, prostaglandins are critical for down regulating TNF-alpha production. Clinical use of cyclooxygenase inhibitors may result in adverse outcomes due to the excessive TNF-alpha production.

Animals↗

PubMed1993

Effect of blood transfusion on immune function. IX. Effect on lymphocyte metabolism.

Blood transfusions have been repeatedly shown to be immunosuppressive in nature. The intracellular mechanisms of this immunosuppression have not been extensively investigated. We investigated the effect of blood transfusions on lymphocyte intracellular metabolism of glucose and amino acids, as well as levels of adenosine deaminase activity and nucleotide triphosphate concentrations. Blood transfusions were found to increase the rate of glucose and glutamine metabolism, to increase nucleotide triphosphate concentrations, and to increase the level of adenosine deaminase activity. This increased level of lymphocyte metabolism in the face of immunosuppression would appear to indicate that the transfusion-induced immunosuppression is an active dynamic process.

Adenosine Deaminase↗

PubMed1993

Evidence for Kupffer cell activation by burn injury and Pseudomonas exotoxin A.

Postburn metabolic and immunological alterations may in part be due to translocation of gut exotoxin and endotoxin, which can result in tumour necrosis factor (TNF) and prostaglandin E (PGE) production by macrophages. We evaluated the effect of burn injury, plus exotoxin and endotoxin on TNF-alpha and PGE production by Kupffer cells, and peritoneal macrophages. Adult Wistar rats underwent 30 per cent TBSA burn or sham burn. Kupffer cells were harvested from rat livers and peritoneal macrophages from the abdominal cavity 24 h postburn. They were cultured overnight at 1 x 10(6) cells/ml and stimulated with saline, 5 micrograms/ml of Pseud. aeruginosa Exotoxin A (Exo-A), 5 micrograms/ml of Pseud. aeruginosa Endotoxin (Endo), Exo-A + Endo, or Exo-A + Endo + the PGE derivative 16,16 dimethyl-PGE (dPGE) (10 micrograms/ml). The supernatants were harvested after 4, 24 and 48 h of culture and assayed for TNF-alpha and PGE. Results showed that burn injury induced an increase in TNF-alpha and PGE production by Kupffer cells stimulated with Exo-A, Endo, and both Exo-A + Endo (P < 0.05). The release of TNF-alpha by Kupffer cells was downregulated by exogenous PGE (P < 0.05). The increased TNF-alpha production was inversely related to PGE levels. In conclusion, both burn injury and Exo-A potentiate the responsiveness of Kupffer cells and peritoneal macrophages to endotoxin as measured by the rate of production of TNF-alpha and PGE. PGE may locally downregulate the immune response by limiting Kupffer cells' and peritoneal macrophages' TNF-alpha production.

ADP Ribose Transferases↗

PubMed1993

Effect of thermal injury and sepsis on neutrophil function.

Burn injury and sepsis have been repeatedly demonstrated to impair the function of circulating (blood) neutrophils. As a result of the difficulty in harvesting and purifying neutrophils from the burn wound, there have been minimal investigations to date on the effect of burn injury and sepsis on the function of neutrophils which have reached the wound. We utilized a sponge matrix model in order to obtain neutrophils from burned and burned-infected rats. Despite having a higher concentration of neutrophils in the blood, both the burned and burned-infected rats were noted to have a decreased number of neutrophils infiltrating the sponge compared with the controls (1.91 +/- 0.30 x 10(6), 2.31 +/- 0.47 x 10(6), and 4.82 +/- 0.64 x 10(6) neutrophils per sponge, respectively). Blood neutrophils from both the burned and burned-infected rats had a greater chemiluminescence capacity than neutrophils from the control group (p < 0.0001). This enhanced capacity was not present with sponge neutrophils obtained from the burned-infected group. The diminished capacity may have been the result of a decreased concentration of prostaglandin E in the sponge fluid of the burned-infected rats compared with that of the burned or control rats (52 +/- 9, 135 +/- 15, and 114 +/- 13 pg/mL of sponge fluid, respectively).

Animals↗

PubMed1993

Effect of ibuprofen on the inflammatory response to surgical wounds.

Patients suffering severe trauma frequently become immunosuppressed following injury. This can predispose patients to infectious sequelae. Biochemically, these patients synthesize excessive quantities of cyclooxygenase products (prostaglandins). It has been hypothesized that the prostaglandins cause the immunosuppression and that inhibition of the cyclooxygenase enzyme could thus prevent the immunosuppression. We investigated the effect of the cyclooxygenase inhibitor ibuprofen on the inflammatory response. Rats were subjected to a 30% total body surface area burn and were administered either ibuprofen for a period of 7 days or 14 days, or were administered the carrier for 14 days. The rats were then killed and multiple immunologic variables were measured. Ibuprofen was found to decrease neutrophil chemiluminescence, lymphocyte blastogenesis, and helper/inducer T-lymphocyte infiltration of a sponge matrix model. The same ibuprofen protocol decreased survival in a cecal ligation and puncture model. In conclusion, the cyclooxygenase enzyme system appears to produce metabolites essential for optimal survival following traumatic injury.

Animals↗

PubMed1993

A review of nutrition support for transplant patients.

Renal, hepatic, and cardiac transplantation are now recognized as acceptable methods for treating end-stage organ failure. Obtaining optimum results in such patients requires not only skillful surgical technique and postoperative immunosuppression but also stabilization of the patient preoperatively. This stabilization includes a number of physiologic parameters. One of the most important of these is the correction of preexisting nutritional deficits. Each type of end-stage organ disease creates unique nutritional problems. This article reviews these deficiencies and makes recommendations as to the appropriate nutrition protocols that can optimize results in the patient who undergoes organ transplantation.

Humans↗

PubMed1992

The Surgical Infection Society's policy on human immunodeficiency virus and hepatitis B and C infection. The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis.

The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis of The Surgical Infection Society has outlined its policy regarding three deadly blood-borne viral infections. The risk of transmission of these microbes, the role of preoperative testing, the problem of the human immunodeficiency virus-infected surgeon, and conduct in the operating room are discussed.

General Surgery↗

PubMed1992

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↗

PubMed1992

Alterations in intracellular lymphocyte metabolism induced by infection and injury.

The effects of burn injury and sepsis on intracellular lymphocyte metabolism were evaluated using a rat model. Adult Lewis rats were subjected to a sham burn, a 30% full-thickness burn, or a 30% full-thickness burn which was infected with Pseudomonas aeruginosa. One week later the animals were sacrificed, and the splenic lymphocytes were harvested and cultured for 24 hr with mitogen stimulation. Lymphocytes from the burned-infected rats were found to utilize more glucose and certain amino acids than did lymphocytes obtained from the other two groups. Lymphocytes obtained from the burned-infected group had lower levels of the immunologically important enzyme, adenosine deaminase, than did the lymphocytes obtained from the other two groups. In summary, sepsis appears to alter a number of intracellular lymphocyte metabolic processes. These alterations may be found to be predictive of early sepsis.

Adenosine Deaminase↗

PubMed1992

Metabolic abnormalities of mitochondrial redox potential in postburn multiple system organ failure.

Forty-five burn patients underwent sequential assays for plasma acetoacetate and beta-hydroxybutyrate concentrations as well as plasma amino acid levels. Those patients who went on to develop multiple system organ failure were noted to have a decrease in their acetoacetate concentration with time, whereas there was no change in those patients who failed to develop multiple system organ failure. The plasma concentration of beta-hydroxybutyrate was not altered by multiple system organ failure. In addition, the plasma acetoacetate/beta-hydroxybutyrate ratio was found to be directly related to the plasma concentration of branched chain amino acids and inversely related to the concentration of aromatic amino acids.

Acetoacetates↗