The application of visible absorption spectroscopy to the analysis of uranium in aqueous solutions.

Through assay analysis into an excess of 1M H2SO4 at fixed temperature a technique has been developed for uranium concentration analysis by visible absorption spectroscopy over an assay concentration range of 1.8-13.4mgU/g. Once implemented for a particular spectrophotometer and set of spectroscopic cells this technique promises to provide more rapid results than a classical method such as Davies-Gray (DG) titration analysis. While not as accurate and precise as the DG method, a comparative analysis study reveals that the spectroscopic method can analyze for uranium in well characterized uranyl(VI) solution samples to within 0.3% of the DG results. For unknown uranium solutions in which sample purity is less well defined agreement between the developed spectroscopic method and DG analysis is within 0.5%. The technique can also be used to detect the presence of impurities that impact the colorimetric analysis, as confirmed through the analysis of ruthenium contamination. Finally, extending the technique to other assay solution, 1M HNO3, HCl and Na2CO3, has also been shown to be viable. Of the four aqueous media the carbonate solution yields the largest molar absorptivity value at the most intensely absorbing band, with the least impact of temperature.

Lung and liver injury following hepatic ischemia/reperfusion in the rat is increased by exogenous lipopolysaccharide which also increases hepatic TNF production in vivo and in vitro.

Hepatic ischemia/reperfusion (I/R) results in tumor necrosis factor (TNF) release. Kupffer cells (KC) are one source of this TNF. This study investigates the effects of hepatic I/R combined with lipopolysaccharide (LPS) on the lung and liver injury that follow hepatic I/R and on hepatic release of TNF, epithelial neutrophil activating protein (ENA-78), and macrophage inflammatory protein-2 (MIP-2). The effects of these experimental conditions on TNF production by primary rat KC in vitro were also investigated. Rats were subjected to hepatic I/R alone, hepatic I/R + LPS, sham laparotomy alone, or sham laparotomy + LPS and pulmonary MPO, pulmonary microvascular permeability, hepatic neutrophil influx, hepatic injury, and hepatic TNF, ENA-78, and MIP-2 production were measured. These experiments demonstrated that hepatic I/R in conjunction with LPS results in a more severe lung and liver injury and increased hepatic TNF, ENA-78, and MIP-2 release. The effects of these experimental conditions on rat KC TNF production demonstrated that hepatic I/R + LPS results in a more significant release of TNF as compared to LPS alone or I/R alone. Hepatic I/R plus LPS results in a more severe lung and liver injury and is likely secondary to a more significant and prolonged release of TNF by KC. This may provide a mechanism for development of multiple organ system failure in some patients undergoing hepatic resection, hepatic transplantation, complex vascular operations, or in the setting of hypovolemic shock. Portal endotoxemia related to mesenteric venous congestion or other systemic insults may have a significant impact on post-operative complications and recovery in the setting of a local or global hepatic I/R injury.

Doctor-patient communication in surgery: attitudes and expectations of general surgery patients about the involvement and education of surgical residents.

BACKGROUND: Education is a major function of academic medical centers. At these teaching institutions residents provide a substantial amount of care on medical and surgical services. The attitudes of patients about the training of surgical residents and the impact of residents on patients' perceptions of care in a surgical setting are unknown. STUDY DESIGN: Patients admitted to the gastrointestinal surgery service completed a 30-item survey designed for this study. Patients included in the study underwent operations and had a postoperative inpatient hospital stay. We analyzed patients' answers to determine frequency and correlations among answers. RESULTS: Two hundred patients participated in the study during a 7-month period between July 1999 and January 2000. A majority of patients were comfortable having residents involved in their care (86%) and felt it was important to help educate future surgeons (91%). Most did not feel inconvenienced by being at a teaching hospital (71%) and felt they received extra attention there (74%). Patients were more willing to participate in resident education if they expected to have several physicians involved in their care, felt that they received extra attention, or if the teaching atmosphere did not inconvenience them. Despite the stated willingness of patients to help with surgical resident education, 32% answered that they would not want residents doing any of their operation. CONCLUSIONS: Surgical resident education is well received and considered important by patients. Patient orientation to the resident education process is vital to patients' perceptions of care and may render patients more willing to participate in educational activities.

Perceived obstacles to career success for women in academic surgery.

HYPOTHESIS: We conducted this study to determine whether concerns expressed by male and female surgeons at 1 academic center are generally reflective of broader concerns for academic surgery and academic medicine. We reviewed published studies concerning women in academic surgery within the context of reporting the results of a survey of both male and female surgeons at 1 academic center. DATA SOURCES: We developed a survey that included demographic information, work experience, and social issues. The survey was distributed to the entire faculty. For key questions, we compared answers between male and female faculty. Additional data came from the published literature. STUDY SELECTION: We reviewed all available studies identified by a MEDLINE search with key words women and academic and medicine or physician. Included studies contained either data collection or editorial comment concerning women in academic medicine. DATA EXTRACTION: Data and opinions from all included studies paralleling survey questions were extracted from each article. DATA SYNTHESIS: Male and female faculty members reported different experiences and perceptions, specifically relating to relationships between family and professional life and perceptions of subtle sex-related biases. Both men and women reported insufficient mentoring and difficulties in balancing personal and professional responsibilities. CONCLUSIONS: Attitudes, behaviors, and traditions surrounding how we structure work and evaluate participation in academic surgery are more difficult to change than just addressing obvious inequities in support for female surgeons. However, attempting the deeper changes is worthwhile, because addressing obstacles faced by female faculty, many of which also affect men, will allow progress toward environments that attract and retain the best physicians, regardless of sex.

Effects of methotrexate on nucleotide pools in normal human T cells and the CEM T cell line.

It has been proposed that the clinical utility of methotrexate (MTX) in the treatment of rheumatoid arthritis may be due, in part, to inhibition of 5-amino imidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT) by polyglutamated forms of MTX. AICARFT is the second folate dependent enzyme in de novo purine biosynthesis. In this study, the effects of MTX on de novo purine biosynthesis as well as total nucleotide pools were evaluated in both the human T cell line, CEM, and phytohemagglutinin-activated normal human T lymphocytes. De novo synthesized purines were metabolically labeled with 14C-glycine after MTX treatment and analyzed by HPLC. In normal T cells, MTX produced a dose-dependent reduction in de novo adenosine and guanosine pools with maximal effects (>50%) at 1 microM MTX. In CEM cells, de novo purine synthesis was almost completely blocked by 1 microM MTX. Total purine pools were also reduced in both cell types after MTX treatment. Since 1 microM MTX caused almost complete growth inhibition in CEM cells, we evaluated whether growth could be reconstituted with exogenous purine bases and pyrimidine nucleosides which can be utilized via salvage pathways. The combination of hypoxanthine and thymidine substantially reversed growth inhibition with 1 microM MTX in CEM cells. Taken together, these results demonstrate that MTX inhibits de novo nucleotide synthesis in T cells and suggest that AICARFT inhibition may be one aspect of the multi-site mechanism of MTX action in the treatment of rheumatoid arthritis.

Difficulty with negative feedback: face-to-face evaluation of junior medical student clinical performance results in grade inflation.

HYPOTHESIS: Direct, face-to-face feedback regarding a medical students' clinical performance will not increase critical, objective analysis of their performance. METHODS: A new ward evaluation system (NS) was used concurrently with our standard written ward evaluation system (OS). The two methods were directly compared using a standard t test. The OS is a subjective written evaluation of clinical performance, with a summary grade of 1-6 given as a final grade, with 1 = fail and 6 = honors. The NS retains the 1-6 grading scale; however, students met with individual faculty and residents and received a face-to-face evaluation of their performance, as well as a written summary. Twenty-four third-year medical students rotating on general surgery at the University of Michigan Medical Center participated in the study. RESULTS: There was a significant degree of grade inflation with the NS, particularly for students with poorer performance. The average grade using the OS was 5.11 +/- 0. 11; with the NS, the average grade was 5.62 +/- 0.07 (P < 0.001). If students with grades of 5.0 or less in the OS are studied, then the average grade using the OS is 4.24 +/- 0.32, in contrast to 5.47 +/- 0.14 with the NS (P < 0.005). An additional interesting finding was noted: among the students who failed to participate in the face-to-face interviews (n = 4), the average grade using the OS was 4.36 +/- 0.29 (P < 0.05 vs OS total). CONCLUSIONS: While students desire more timely, direct feedback on their clinical performance, faculty are poor at giving direct, objective, face-to-face feedback, particularly when it involves negative feedback, with resultant grade inflation.

The ratio of ELR+ to ELR- CXC chemokines affects the lung and liver injury following hepatic ischemia/ reperfusion in the rat.

Hepatic ischemia/reperfusion (I/R) results in a neutrophil-dependent lung and liver injury. The process of neutrophil recruitment and activation in this injury is at least partially dependent on the presence of the ELR+ CXC chemokines. Other investigations have shown that ELR- CXC chemokines can block ELR+ CXC chemokine neutrophil recruitment and activation in vitro. To begin to investigate the role of the balance between these 2 types of molecules in vivo in neutrophil recruitment and activation following hepatic I/R, we used our rat model of lobar hepatic I/R and pretreated animals with pharmacologic doses of gamma-interferon (gamma-IFN). gamma-IFN is known to upregulate some of the ELR- CXC chemokines, including gamma-IFN-inducible protein (IP-10) and monokine-induced by gamma-IFN (MIG), as well as down-regulate ELR+ CXC chemokine production. Following hepatic I/R or sham laparotomy, hepatic and pulmonary levels of the ELR- chemokines, IP-10 and MIG, and the ELR+ chemokines, rat cytokine-induced neutrophil chemoattractant (KC), macrophage inflammatory protein-2 (MIP-2), and epithelial neutrophil activating protein (ENA-78) were determined by ELISA, and lung and liver injury were assessed. In response to gamma-IFN, hepatic and pulmonary levels of the ELR- chemokines were increased and the levels of the ELR+ chemokines were decreased. Immunohistochemical staining confirmed the hepatocyte as the source of these molecules, as well as the changes in chemokine levels in response to gamma-IFN. There was an associated significant decrease in liver and lung injury, although there was no significant decrease in neutrophil influx in either tissue. This suggests that the alteration in the balance of ELR+ to ELR- CXC chemokines results in a decrease in tissue injury through a mechanism other than through an alteration in tissue neutrophil levels.

The role of chemokines in the immunopathology of the liver.

Chemokines are small protein inflammatory mediators that were classically known for their elicitation of inflammatory cells out of the vasculature. However, more contemporary studies show that these ubiquitous factors impinge on many facets of biology, including hematopoiesis, angiogenesis, and mitogeneis. The elucidation of mechanisms involved in the immunopathogenesis of liver disease has magnified the importance of chemokines in this organ. Accordingly, a number of in vitro and in vivo studies have highlighted the importance of chemokine biology in both acute and chronic liver disease, and a variety of liver diseases have been shown to involve chemokines and their receptors during the initiation and main tenance of liver pathology. A greater understanding of the role chemokines play during liver disease may permit the employment of therapies that target or enhance chemokines in the liver. This review will highlight the current clinical and experimental research in the immunopathogenesis of acute and chronic liver diseases.

Novel CXCR2-dependent liver regenerative qualities of ELR-containing CXC chemokines.

Severe acute liver injury due to accidental or intentional acetaminophen overdose presents a major clinical dilemma often requiring liver transplantation. In the present study, liver regeneration after profound liver injury in mice challenged with acetaminophen was facilitated by the exogenous addition of ELR-containing CXC chemokines such as macrophage inflammatory protein-2 (MIP-2), epithelial neutrophil-activating protein-78 (ENA-78), or interleukin 8. Intravenous administration of ELR-CXC chemokines or N-acetyl-cysteine (NAC) immediately after acetaminophen challenge in mice significantly reduced histological and biochemical markers of hepatic injury. However, when the intervention was delayed until 10 h after acetaminophen challenge, only ELR-CXC chemokines significantly reduced liver injury and mouse mortality. The delayed addition of ELR-CXC chemokines to cultured hepatocytes maintained the proliferation of these cells in a CXCR2-dependent fashion after acetaminophen challenge whereas delayed NAC treatment did not. These observations demonstrate that ELR-CXC chemokines represent novel hepatic regenerative factors that exhibit prolonged therapeutic effects after acetaminophen-induced hepatotoxicity.

Proliferative effects of CXC chemokines in rat hepatocytes in vitro and in vivo.

The CXC chemokines have well-documented neutrophil chemotactic, angiogenic, and mitogenic properties. The current investigations evaluate the effects of interleukin-8 (IL-8), epithelial neutrophil activating protein (ENA-78), and macrophage inflammatory peptide-2 (MIP-2) on hepatocyte proliferation in vitro and liver regeneration in vivo. Primary rat hepatocytes were isolated by collagenase digestion and exposed to incremental doses of IL-8, ENA-78, or MIP-2, and cellular proliferation was measured via tritiated thymidine incorporation. These experiments demonstrated significant increases in hepatocyte proliferation in response to IL-8, ENA-78, and MIP-2. Next, rats were sacrificed in a time-dependent manner following 70% hepatectomy or sham laparotomy, and hepatic tissue levels of MIP-2 and ENA-78 were measured using an ELISA. ENA-78 and MIP-2 were significantly elevated following 70% hepatectomy as compared with sham-operated control animals. Rats undergoing 70% hepatectomy were then treated with neutralizing anti-ENA-78 serum, anti-MIP-2 serum, or preimmune control serum, and liver regeneration was evaluated. These experiments demonstrated that neutralization of ENA-78 or MIP-2 slowed the rate of liver regeneration. These data suggest that the CXC chemokines may be important agents for the induction of hepatocyte proliferation and may be important molecules in vivo in the setting of liver injury, repair, and regeneration.

Tumor necrosis factor up-regulates intercellular adhesion molecule 1, which is important in the neutrophil-dependent lung and liver injury associated with hepatic ischemia and reperfusion in the rat.

Tumor necrosis factor (TNF) is released during hepatic ischemia/reperfusion (I/R) and plays an important role in the ensuing neutrophil-mediated lung and liver injury. Since TNF is not a direct neutrophil chemotaxin, we hypothesized that TNF may up-regulate neutrophil adhesion molecules, specifically intercellular adhesion molecule-1 (ICAM-1), following hepatic I/R, and that this molecule then plays an important role in tissue neutrophil influx. Rats underwent 90 min of lobar hepatic ischemia with reperfusion. Pulmonary and hepatic ICAM-1 expression were assessed by reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemical staining. Increases in hepatic ICAM-1 were demonstrated within 1 h of reperfusion, while increases in pulmonary ICAM-1 were not seen until 6 h of reperfusion. Next, rats were treated with anti-TNF antibody or control antibody without TNF neutralizing properties prior to hepatic I/R. Pretreatment with anti-TNF antibody significantly decreased pulmonary and hepatic ICAM-1 expression after hepatic I/R. We next investigated the effects of pretreatment with anti-ICAM-1 antibodies on the lung and liver injury that follows hepatic I/R. Lung injury was assessed by changes in pulmonary capillary permeability as estimated by extravasation of Evans Blue dye and pulmonary neutrophil influx as measured by lung myeloperoxidase levels. Liver injury was assessed by hepatic neutrophil morphometrics and plasma liver enzymes (alanine aminotransferase). Pretreatment with anti-ICAM-1 antibodies significantly decreased pulmonary capillary permeability, pulmonary myeloperoxidase, hepatic neutrophil influx, and plasma alanine aminotransferase, as compared to animals pretreated with control antibody. These data suggest that TNF is a proximal trigger for pulmonary and hepatic ICAM-1 up-regulation following hepatic ischemia with reperfusion, and that ICAM-1 is important for pulmonary and hepatic neutrophil influx, with the resultant tissue injury, following hepatic I/R.

Safety and long-term durability of completion gastrectomy in 81 patients with postsurgical gastroparesis syndrome.

Postsurgical gastroparesis syndrome (PGS) is characterized by postcibal nausea and vomiting and is associated with functional gastric dysmotility. Patients frequently present with marked weight loss and malnutrition requiring hospitalization and prolonged parenteral nutrition. Typically, these patients fail to respond to prokinetic agents. Gastric reoperations are frequent and usually unsuccessful. Near-completion gastrectomy (NCG) has proved useful in small series of patients, but long-term follow-up has been lacking. The purpose of this study is to assess the safety and durability of NCG in a large group of patients with PGS. Eighty-one patients with documented PGS who failed to respond to prokinetic drug therapy were treated with NCG over an 11-year period. NCG was standardized with a 55-cm Roux-en-Y reconstruction. Patients were evaluated by a retrospective chart review and a prospective phone interview that compared pre- and postoperative health status based on a standardized severity of symptoms score. There were no operative deaths or complications related to the anastomosis. Average patient follow-up was 56.1 months (range, 2-142 months). Fifteen patients died of unrelated causes, and 14 patients were lost to follow-up. The remaining 52 patients showed a significant overall decrease in severity of symptoms score largely due to reduction in gastrointestinal symptoms and to a smaller but significant reduction in systemic symptoms. Nearly 80 per cent of patients reported long-term relief of symptoms. NCG is the procedure of choice for carefully selected patients with documented. Low morbidity and durable results can be anticipated in the majority of patients.

Hepatic inflammation following 70% hepatectomy may be related to up-regulation of epithelial neutrophil activating protein-78.

Tumor necrosis factor-alpha (TNF) is known to be released after partial hepatectomy. Furthermore, TNF triggers the release of chemotactic cytokines, such as epithelial neutrophil activating protein (ENA-78), which are important for neutrophil chemotaxis, activation, and propagation of the inflammatory response. We now postulate that ENA-78 may play a role the hepatic inflammatory response that occurs following partial hepatectomy. Rats were subjected to 70% hepatectomy or sham laparotomy and were killed in a time-dependent manner. Hepatic neutrophil influx, as assessed by myeloperoxidase (MPO) levels, serum alanine aminotransferase (ALT), and hepatic TNF and ENA-78 levels, as measured by ELISA, were evaluated at 1, 6, and 12 h following operation. MPO levels became significantly elevated within 6 h of hepatectomy and remained elevated at 12 h. Serum ALT became significantly elevated within 1 h of hepatectomy and continued to rise at 12 h. Hepatic TNF and ENA-78 were also increased significantly after hepatectomy. Next, rats undergoing 70% hepatectomy were treated with neutralizing anti-ENA-78 serum; this resulted in a significant decrease in hepatic MPO and serum ALT, suggesting less hepatic injury. To determine whether ENA-78 release was induced by TNF is this model, rats were treated with neutralizing anti-TNF serum and hepatic ENA-78 levels measured 6 h posthepatectomy. ENA-78 levels were significantly decreased in the animals receiving the anti-TNF serum, suggesting that ENA-78 is released in response to TNF in this model. These data suggest that TNF triggers the release of ENA-78 following 70% hepatectomy and that ENA-78 contributes to the hepatic neutrophil influx and liver injury following 70% hepatectomy.

Post-ischemic shunt following hepatic ischemia/reperfusion does not affect tissue chemokine levels of tissue injury.

Hepatic ischemia followed by reperfusion causes the release of a cascade of mediators, including tumor necrosis factor-alpha and epithelial neutrophil activating protein (ENA-78), which are important in the subsequent development of the lung and liver injury associated with this insult. We hypothesize that preferential post-ischemic shunting of blood into the nonischemic hepatic lobes at the time of reperfusion may increase the ischemic injury. To test this hypothesis, we utilized a rat model of lobar no-flow hepatic ischemia/reperfusion and removed the nonischemic hepatic lobes at the time of reperfusion to eliminate the preferential shunting of blood into the nonischemic tissues. We assessed pulmonary and hepatic tissue levels of ENA-78, pulmonary neutrophil influx and changes in pulmonary capillary permeability, and liver injury as measured by hepatic neutrophil influx and serum transaminase levels. Our results demonstrated that there were no significant differences in pulmonary and hepatic levels of ENA-78, or in the development of the lung and liver injury in animals undergoing resection of the nonischemic hepatic lobes at the time of reperfusion, as compared with animals undergoing hepatic ischemia/reperfusion alone.

The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat.

The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and have shown that this injury induces the production and release of hepatic-derived tumor necrosis factor alpha (TNF-alpha), which mediates, in part, local liver injury following hepatic reperfusion. In the present study, we have extended these previous observations to assess whether an interrelationship exists between TNF-alpha and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein, that may account for some of the pathology of neutrophil-mediated ischemia/reperfusion-induced liver injury. We observed that hepatic ischemia/reperfusion injury leads to: (1) a coincident increase in hepatic neutrophil sequestration, elevated serum alanine aminotransferase (ALT) levels, and hepatic production of epithelial neutrophil activating protein; (2) passive immunization with neutralizing antibodies to TNF-alpha resulted in significant suppression of hepatic-derived epithelial neutrophil activating protein; and (3) neutralization of epithelial neutrophil activating protein by passive immunization significantly attenuated neutrophil sequestration in the liver and serum ALT levels. These findings support the notion that local expression of hepatic epithelial neutrophil activating protein produced in response to TNF-alpha is an important mediator of the local neutrophil-dependent hepatic injury associated with hepatic ischemia/reperfusion.

Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein.

The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. One of the striking consequences of liver injury is the associated pulmonary dysfunction that may be related to the release of hepatic-derived cytokines. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and demonstrated that this injury causes the production and release of hepatic-derived TNF, which mediates a neutrophil-dependent pulmonary microvascular injury. In this study, we have extended these previous observations to assess whether an interrelationship between TNF and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein-78 (ENA-78), exists that may be accountable for the pathology of lung injury found in this model. In the context of hepatic ischemia/reperfusion injury, we demonstrated the following alterations in lung pathophysiology: (a) an increase in pulmonary microvascular permeability, lung neutrophil sequestration, and production of pulmonary-derived ENA-78; (b) passive immunization with neutralizing TNF antiserum resulted in a significant suppression of pulmonary-derived ENA-78; and (c) passive immunization with neutralizing ENA-78 antiserum resulted in a significant attenuation of pulmonary neutrophil sequestration and microvascular permeability similar to our previous studies with anti-TNF. These findings support the notion that pulmonary ENA-78 produced in response to hepatic-derived TNF is an important mediator of lung injury.

Desferal attenuates TNF release following hepatic ischemia/reperfusion.

Iron chelators have been shown to protect against oxygen free radical injury occurring in association with ischemia/reperfusion (I/R). Tumor necrosis factor alpha (TNF) represents a major mediator of the pulmonary and hepatic injury occurring after hepatic I/R since pretreatment with anti-TNF antibody results in significant protection against both the lung and liver injury following this insult. We were therefore interested in the possible association of the protective actions of deferoxamine (Desferal) following hepatic I/R and subsequent TNF release. A rat model of hepatic I/R was used to evaluate this; four experimental groups were studied. Animals in I/R underwent 90 min of hepatic ischemia with subsequent reperfusion. DES-I/R animals were pretreated with 200 mg of deferoxamine and VEH-I/R rats were given an equivalent amount of vehicle prior to hepatic I/R. SHAM animals underwent sham laparotomy alone. Plasma specimens were obtained and analyzed for TNF using a cytolytic bioassay based on the WEHI 164 subclone 13 cell line. Mean peak TNF levels following deferoxamine pretreatment was 110.38 +/- 24.68 pg/ml, as compared to mean peak TNF levels of 213.64 +/- 38.09 pg/ml in the VEH-I/R group (P < 0.01). Lung injury following hepatic I/R was evaluated by assessment of pulmonary microvascular permeability and by evaluation of pulmonary neutrophil infiltration as measured by pulmonary myeloperoxidase (MPO) content. Pretreatment with deferoxamine resulted in a significant decrease in lung leak as compared to animals pretreated with vehicle prior to I/R (DES-I/R = 0.192 +/- 0.013, VEH-I/R = 0.690 +/- 0.050; P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

LPS pretreatment protects from hepatic ischemia/reperfusion.

In vivo administration of nonlethal doses of lipopolysaccharide (LPS) to rodents can result in protection from subsequent lethal doses of endotoxin or LPS. We have previously demonstrated that hepatic ischemia/reperfusion (I/R) results in a TNF-dependent lung and liver injury and we postulated that pretreatment with sublethal concentrations of LPS prior to hepatic I/R could be protective from this injury. To test this hypothesis, five groups of rats were studied. LPS-I/R received 25 micrograms of LPS i.v. 24 hr prior to I/R, VEH-I/R received an equivalent volume of vehicle iv 24 hr prior to I/R, LPS-LPS received 25 micrograms of LPS i.v. 24 hr prior to sham laparotomy at which time an additional 25 micrograms of LPS was given i.v., VEH-LPS received an equivalent volume of vehicle 24 hr prior to sham laparotomy and 25 micrograms of LPS i.v. immediately prior to sham laparotomy, and SHAM consisted of sham-operated control animals. Peak plasma tumor necrosis factor-alpha (TNF) levels occurred between 30 and 150 min of reperfusion: LPS-I/R = 778 +/- 150 pg/ml (n = 5), VEH-I/R = 145 +/- 46 pg/ml (n = 5), LPS-LPS = 970 +/- 716 pg/ml (n = 4), VEH-LPS = 15,949 +/- 10,937 (n = 5), and SHAM = 3 +/- 1 (n = 5). As previously demonstrated by other investigators, pretreatment with LPS decreases TNF release in response to a second dose of LPS; however, TNF release was increased following hepatic I/R in those animals pretreated with LPS (LPS-I/R vs VEH-I/R, P = 0.014).(ABSTRACT TRUNCATED AT 250 WORDS)