Changes In Organ Function Research Articles

A proposed solution to the clinical assessment of sarcoidosis: The sarcoidosis three-dimensional assessment instrument (STAI)

The clinical assessment of sarcoidosis has been confounded by its inexact diagnostic criteria, multiorgan involvement, and effects of therapy. In this manuscript an instrument, the Sarcoidosis Three-Dimensional Assessment Instrument (STAI), is proposed to assess the clinical state of sarcoidosis. The instrument examines each organ involved with sarcoidosis separately. For each organ, the instrument contains three axes: involvement, severity, and activity. Involvement is based upon a previously described instrument that has been updated to capture involvement of more organs and to account for advances in diagnostic testing for sarcoidosis. Severity is based both on the decline from normal capacity as well as physical and psychosocial limitation. Disease activity takes into account changes in organ function as well as changes in therapy. Although this instrument is presently not validated, it is hoped that it will undergo study as it rationally accounts for several problems of previous assessment instruments.

Daily evaluation of organ function during renal replacement therapy in intensive care unit patients with acute renal failure

Purpose The aim of this study was to assess changes in organ function in acute renal failure patients during renal replacement therapy and relate them to outcome. Materials and Methods Medical and nursing charts from 111 patients with acute renal failure who underwent renal replacement therapy (hemodialysis or hemofiltration) from July 2000 until July 2002 on a 31-bed medicosurgical intensive care unit (ICU) at a university hospital in Belgium and in whom the Sequential Organ Failure Assessment (SOFA) score was calculated daily before the start of therapy until the seventh day, or the end of therapy, were analyzed. Changes in SOFA score over time (Δ SOFA) were calculated. Results Of 111 patients, 63 (57%) died in the ICU. Nonsurvivors were older (68 [52-76] vs 59 [48-70] years, P = .017) and had initially higher respiratory, cardiovascular, and total SOFA scores compared with survivors. A greater Δ renal SOFA at 24 hours was associated univariantly with a higher risk of ICU mortality (odds ratio, 1.7; 95% confidence interval, 1.2-2.6; P = .013). In a multivariate analysis with ICU outcome as the dependent variable, only age, cardiovascular SOFA score on admission, and the change in total SOFA score over the first 24 hours were independently associated with a greater risk of death. Conclusions Assessment of these factors in the first 24 hours of renal replacement therapy could help identify patients at higher risk of mortality early during their ICU admission.

Influences of Norepinephrine Transporter Function on the Distribution of Sympathetic Activity in Humans

Previous studies suggest that neuronal norepinephrine transporter function may regulate the distribution of sympathetic activity among blood vessels, heart, and kidney; we tested the functional relevance in humans. Sixteen healthy men (26+/-1 years) ingested 8 mg of the selective norepinephrine reuptake transporter inhibitor reboxetine or a matching placebo on 2 separate days in a double-blind, randomized, crossover fashion. We monitored heart rate, thoracic bioimpedance, blood pressure, glomerular filtration rate, and renal blood flow. Ninety minutes after ingestion of the test medication, subjects were tilted to a 45 degrees head-up position, where they remained for an additional 30 minutes. Reboxetine increased supine systolic blood pressure through an increase in cardiac output whereas systemic vascular resistance decreased. Furthermore, reboxetine increased heart rate, particularly with a head-up tilt. Supine plasma renin activity was 0.71+/-0.15 ng angiotensin (Ang)/L per mL/h with placebo and 0.36+/-0.07 ngAng/L per mL/h with reboxetine (P<0.01). Supine plasma Ang II concentrations were also decreased with reboxetine. Both plasma renin activity and Ang II concentrations remained suppressed during head-up tilt. On placebo, renal vascular resistance increased with head-up tilt. The response was abolished with norepinephrine reuptake inhibition. We conclude that norepinephrine reuptake function profoundly influences the distribution of sympathetic activity between the heart, vasculature, and kidney in humans. All of these changes are physiologically relevant because they lead to corresponding changes in organ function.

Early changes in organ function predict eventual survival in severe sepsis*

Early identification and treatment of severe sepsis can significantly reduce mortality rate. We hypothesized that a risk prediction model based on early (baseline to day 1 of study) response to standard care should be significantly related to 28-day survival. Analysis of organ dysfunction data from two placebo-controlled severe sepsis trials (PROWESS and secretory phospholipase A2 inhibitor trials). Research laboratory. The placebo arms of two randomized, double-blind sepsis trials were combined (n = 1036). These patients met criteria for severe sepsis and received supportive standard intensive care and fluid resuscitation. None. Sequential Organ Failure Assessment (SOFA) scores were calculated daily using the most aberrant physiologic or laboratory variables. Baseline and post-baseline SOFA scores categorized as improved, unchanged, or worsened were used in regression analyses correlating organ dysfunction changes with 28-day mortality. Improvement in cardiovascular (p = .0010), renal (p < .0001), or respiratory (p = .0469) function from baseline to day 1 was significantly related to survival. Odds ratios (95% confidence intervals) associated with improved vs. worsened respiratory, cardiovascular, or renal function before start of day 1 were 0.56 (0.35-0.91), 0.33 (0.18-0.59), and 0.30 (0.17-0.52), respectively. Continued improvement in cardiovascular function before start of day 2 and start of day 3 was associated with further improvement in survival (p <. 0001), with odds ratios of 0.15 (0.06-0.39) and 0.11 (0.04-0.31) for patients who improved compared with those who worsened. No other organ system was retained in the model, and improvement beyond day 1 in any other organ function did not add to the model's predictive power. These analyses suggest that outcomes for patients with severe sepsis are closely related to early (baseline to day 1 here) improvement, or lack thereof, in organ function. Also, clinical improvement on subsequent days may have little additional impact on the likelihood of survival.

Selective inducible nitric oxide synthase inhibition attenuates organ dysfunction and elevated endothelin levels in LPS‐induced DIC model rats

We examined the role of nitric oxide (NO) produced by an inducible isoform of NO synthase (iNOS) using N[6]-(iminoethyl)-lysine (L-NIL), a selective iNOS inhibitor, in the rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) and investigated changes in organ function, plasma levels of NOX (metabolites of NO) and endothelin. We induced experimental DIC by the sustained infusion of 30 mg kg(-1) LPS for 4 h via the tail vein. We then investigated the effect of L-NIL (6 mg kg(-1), from - 0.5 to 4 h) on LPS-induced DIC. Blood was withdrawn at 4 and 8 h, and all four groups (LPS with or without L-NIL at 4 and 8 h) consisted of eight rats. Three of the animals in the 8-h LPS group died, and we examined blood samples from five rats in this group. None of the other rats died. The LPS-induced elevation of creatinine, alanine aminotransferase, glomerular fibrin deposition and plasminogen activator inhibitor was significantly suppressed by L-NIL coadministration, although L-NIL did not affect the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of the D-dimer that reflect the lysis of cross-linked fibrin were significantly increased by L-NIL coadministration in the LPS-induced DIC model. Plasma levels of NOX and endothelin were obviously increased by LPS infusion. However, both levels were significantly suppressed in the LPS + L-NIL group, when compared with the LPS group. Although mean arterial pressure (MAP) was significantly decreased between 2 and 8 h compared with the control in the LPS group, this depression was significantly attenuated in the LPS + L-NIL group. Our results suggest that NO induced by iNOS contributes to hypotension (depressed MAP), the progression of hepatic and renal dysfunction, microthrombus deposition and elevated endothelin levels in the rat model of LPS-induced DIC.

Critical care and monitoring of small animal patients

ONCE patient triage and emergency procedures are complete, attention must turn to the longer-term care of critically ill animals. Such cases are typically unstable and profound changes in organ function...

Surgical considerations in the geriatric patient

The geriatric patient has a high incidence of foot deformities and may be considered a good surgical candidate if healthy and psychologically ready for the surgical procedure. Foot problems in the geriatric population that may require surgical intervention can be grouped into approximately five categories, including (1) localized orthopedic disorders (ie, bunions, hammer toes, and so on); (2) skin and nail problems (ie, onychomycosis); (3) degenerative and inflammatory arthritis; (4) diabetic foot disorders; and (5) neuromuscular disease. However, age-related changes in cardiovascular, pulmonary, and renal function increase the risk of perioperative complications. The higher rates of complications seen in the older surgical patients result in part from existing comorbidity and age-associated changes in organ function. Extensive procedures depending on good bone healing for success should usually not be attempted on older patients. Office surgery for the geriatric patient should involve only the simplest procedures and should be kept to a minimum because of the increased possibility of postoperative complications. In the hospital there is better preoperative evaluation, operating room conditions, and postoperative care.

Oxygen debt criteria quantify the effectiveness of early partial resuscitation after hypovolemic hemorrhagic shock.

The effectiveness of partial resuscitation after hypovolemic hemorrhagic shock with deferment of full resuscitation is critical to successful hypotensive resuscitation. To quantitatively address this issue, 40 canines were bled under anesthesia to a mean oxygen debt (O(2)D) of 104 +/- 7.6 mL/kg over 60 minutes (mortality, 40%). Animals surviving the shock were then immediately resuscitated with 0%, 8.4%, 15%, 30%, or 120% (full resuscitation) of shed volume as 5% albumin and held for 2 hours postshock, when the remaining portion of full resuscitation volume was given. Animals were followed for 7 days postshock with hepatic and renal function studies, and then, under anesthesia, cardiac output and organ biopsy specimens were taken before the animals were killed. By 2 hours postshock, 0% immediate resuscitation had an O(2)D increase of 80 mL/kg above end of shock, but O(2)D at 8.4% immediate resuscitation decreased -30 mL/kg, 15% immediate resuscitation fell -65 mL/kg, 30% immediate resuscitation decreased -80 mL/kg below end of shock, and O(2)D with 120% full resuscitation fell to preshock levels. All decreases in O(2)D were significantly (p < 0.05) below end of shock, but both 15% and 30% immediate resuscitation exceeded the 8.4% immediate resuscitation rate (p < 0.05) throughout the resuscitation, and 120% full resuscitation exceeded these (p < 0.05). The immediate resuscitation O(2)D response correlated significantly (p < 0.001) with base deficit and lactate, but blood pressure was not a significant discriminator. Seven-day biopsies showed return of bowel mucosa but a pattern of cellular injury in heart, liver, and kidney that improved from 8.4% < 15% < 30 < 120% immediate resuscitation. The data suggest that, compared with 120% postshock immediate resuscitation, 8.4% and 15% immediate resuscitation give poorer results, with 30% immediate resuscitation showing mild, transient, but acceptable changes in organ function allowing for a 2-hour delay until full resuscitation, with complete 7-day recovery. Base deficit and lactate, but not blood pressure, are significant indices of O(2)D.

Aeromonas Causes Severe Skin Lesions in Rainbow Trout (Oncorhynchus mykiss): Clinical Pathology, Haematology, and Biochemistry

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Cytokines and inflammatory pathways in the pathogenesis of multiple organ failure following abdominal aortic aneurysm repair.

Multiple organ failure is a common mode of death following abdominal aortic aneurysm repair, particularly after rupture. Cytokines are the principal mediators of the inflammatory response to injury and high levels of circulating cytokines have been associated with poor outcome in major trauma and sepsis. Abdominal aortic aneurysm repair results in an ischaemia-reperfusion injury to the tissues distal to the site of aortic clamping. The inflammatory response in these tissues causes the release of cytokines, principally Interleukins 1-beta, 6, and 8, and Tumour Necrosis Factor alpha. If released in large enough concentrations, these cytokines may enter the circulation and gain access to organs distant to the site of initial injury. Circulating cytokines cause dysfunction of the renal, cardiovascular, respiratory, nervous and musculo-skeletal systems. The combination of these individual changes in organ function is the multiple-organ dysfunction syndrome, which may progress to multiple organ failure.

Improvement of multiple organ functions in hepatorenal syndrome during albumin dialysis with the molecular adsorbent recirculating system.

Recently, significant improvement of renal function and prolongation of survival were reported in hepatorenal syndrome (HRS) patients treated with the Molecular Adsorbent Recirculating System (MARS). As no impact on extrarenal organ function was documented, this trial looked into multiple organ function changes during MARS in HRS patients. Eight HRS patients (4 male, mean age 42.1 years, range 30-58, all United Network for Organ Sharing [UNOS] status 2A) were treated intermittendly 4-14 times (total 47, mean 5.9 +/- 3.4) between 4 and 8 h/single treatment. The following changes were observed pre- and posttreatment: bilirubin 466 +/- 146 to 284 +/- 134 micromol/L, creatinine 380 +/- 182 to 163 +/- 119 micromol/L, urea 26.4 +/- 10.3 to 12.9 +/- 4.9 mmol/L, plasma sodium 127.5 +/- 7.7 to 137.5 +/- 4.8 mmol/L (all p < 0.01). Mean arterial pressure (MAP) increased from 71.9 +/- 12.8 to 95.6 +/- 7.8 Torr (p < 0.001). Oliguria or anuria, present in all patients, was successfully reverted. Ascites, present in all patients, was not detectable after the treatment period. The hepatic encephalopathy grade decreased from 2.8 +/- 0.8 to 0.8 +/- 0.7 (p < 0.0001). Child-Index decreased from 13.25 +/- 1.3 to 9.4 +/- 1.8 (p < 0.001). The hospital survival rate was 62%. One man underwent successful liver transplantation 18 months after the treatment. We conclude that MARS can improve multiple organ functions in patients with HRS.

Influence of age and comorbidities on the chemotherapeutic management of lung cancer

More than 60% of all patients with cancer are currently older than 65 years. Correspondingly, the peak of lung cancer incidence is reached in the age group between 75 and 80 years. As a consequence to this ageing patient population, three factors become of major importance for the chemotherapeutic management of lung cancer, namely functional status, age-specific phenomenon and the presence of comorbidities. While the functional status is dependent on physiological changes in organ function, ageing-specific phenomena include depression, alterations of mental status, reduced nutritional status and missing social support. Comorbidities frequently have a risk profile comparable to that of lung cancer. Clinical studies with a special focus on elderly patients are still rare. In small-cell lung cancer retrospective analyses have demonstrated that age alone is not a major prognostic factor compared to performance status, tumor stage or gender. Nevertheless elderly patients with lung cancer are still frequently excluded from clinical trials, and receive less optimal or even no chemotherapeutic treatment at all. Studies evaluating less aggressive treatment figured out that single agent therapy with etoposide is inferior compared to combination chemotherapy in patients with small cell lung cancer (SCLC). In elderly patients with non-small cell lung cancer (NSCLC), single agent treatment with vinorelbine plus ‘Best Supportive Care’ was significantly superior to ‘Best Supportive Care (BSC)’ alone; with respect to survival and symptom palliation.

Therapy of acute myeloid leukemia in the elderly patient

Incidence and mortality rates of acute myeloid leukemia (AML) increase exponentially with advancing age. AML diagnosed in elderly patients differs from that diagnosed in younger patients. But not only disease-specific differences are important. Treating elderly patients with AML age-associated differences in the patients general presentation, such as physiological changes in organ function, decreased ability to react to stress, dependence in activities of daily living, existence of other morbidities (co-morbidity), the need to take drugs for those diseases and the reduced life expectancy can force alterations in the disease management. Clinical trials for the treatment of AML have been excluding elderly patients for years. Even trials accepting elderly patients with AML did select the group of otherwise healthy elderly patients for participation in the trial. Thus the data for AML management in elderly patients do not reflect the whole group of elderly patients with AML. If the patient is treated with curative intention, therapy of choice is the so-called 3 + 7 protocol for induction of complete remission, followed by a consolidation therapy and in some cases by maintenance therapy. In some situations, especially in very old patients, a palliative intention to treatment is favored. There are no generally accepted criteria to measure treatment benefit in this setting nor established chemotherapy protocols for this situation. Further trials for elderly patients with AML have to offer treatment options for the whole group of patients and have to determine what treatment approach is the best for which individual patient.

Fourier transform infrared study of the effect of diabetes on rat liver and heart tissues in the CH region

Diabetes mellitus is characterized by hyperglycemia, a relative lack of insulin. The metabolic disturbances in diabetic patients are often associated with cardiac and liver dysfunctions. Generally, experimental diabetic models in animals have been used to study diabetes-related changes in organ function, but the complexity of intact tissues can cause contradictory results. For this reason, different techniques have been used to understand the mechanisms of these dysfunctions in diabetic organs. The purpose of the present study is to investigate the effects of streptozotocin (STZ)-induced diabetes on rat liver and heart tissues at the molecular level by Fourier Transform Infrared (FTIR) spectroscopy. Wistar rats of both sexes, weighing 200–250 g, were made diabetic by a single injection of 50 mg kg −1 intraperitoneal (i.p.) streptozotocin dissolved in 0.05 M citrate buffer (pH 4.5) and they were kept for 4–5 weeks. The diabetes status was checked by measuring the blood glucose level. In the complex FTIR spectra, the bands in the CH region for example the CH 2 antisymmetric and symmetric stretching, the CH 3 symmetric and asymmetric stretching vibrations due to lipids and proteins in the 3000–2800 cm −1 region and CH 2 scissoring around 1464 cm −1 and the CH 3 scissoring at 1454 cm −1 were analyzed. Characteristic spectral bands of these diabetic samples were compared with those of control group to confirm the effect of diabetes on liver and heart tissues. The FTIR spectra revealed dramatic differences in the band positions and bandwidths, signal intensity values and signal intensity ratios between diabetic and control tissues. Similar differences were observed for diabetic liver and heart tissues. A significant increase in the bandwidth of the CH 2 symmetric and antisymmetric stretching and the CH 3 symmetric and asymmetric stretching bands has been observed for both tissue types. The wavenumber of the CH 3 asymmetric stretching band shifts to lower values, indicating an increase in the order in the deep interior part of the lipid chains. The ratio of the CH 2 symmetric to CH 3 symmetric stretching band (lipid/protein ratio) decreases by 13% for diabetic heart and liver tissues. A decrease is also detected in the ratio of the CH 2 scissoring to the CH 3 scissoring mode. The overall intensity of these bands is seen to increase for diabetic tissues.

Induction of organ dysfunction and up-regulation of inflammatory markers in the liver and kidneys of hypotensive brain dead rats: a model to study marginal organ donors.

Marginal donors exposed to the full array of effects induced by brain death are characterized by low success rates after transplantation. This study examined whether organs from marginal brain dead animals show any change in organ function or tissue activation making them eventually more susceptible for additional damage during preservation and transplantation. To study this hypothesis we first focused on effects of brain death on donor organ quality by using a brain death model in the rat. After induction of brain death, Wistar rats were ventilated for 1 and 6 hr and then killed. Sham-operated rats served as controls. Organ function was studied using standard serum parameters. Tissue activation of liver and kidney was assessed by staining of immediate early gene products (IEG: FOS, JUN), and inflammatory markers; cell adhesion molecules (Intercellular adhesion molecule-1, vascular cell adhesion molecule-1), leukocyte infiltrates (CD45, T cell receptor, CD8, CD4), and MHC class II. During brain death progressive organ dysfunction was observed that coincided with a significant increase in activation of immediate early genes, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD45, and MHC class II versus nonbrain dead controls. In liver tissue also the markers for T cell receptor and CD8 significantly increased. These findings suggest that an immune activation with increased endothelial cell activation and immediate early gene expression occurs in marginal donors after brain death induction. We suggest that brain death should not longer be regarded as a given nondeleterious condition but as a dynamic process with potential detrimental effects on donor organs that could predispose grafts for increased alloreactivity after transplantation.

Health effects of exposure to ambient carbon monoxide

Atmospheric trace gases such as carbon monoxide (CO) are essential for the healthful function of the Earth’s plants, animals, and natural environment. Biological organisms not only adapt to background levels of CO, but also produce and utilize CO for normal life processes. Increasing concentrations of CO from man-made sources became a public health problem, however, when levels disturbed the established natural balances. Unfortunately, the common atmospheric gases are not always taken seriously as environmental “pollutants”. Concerns about the potential health effects of exposure to CO have been addressed in extensive studies with various animal species as subjects. Under varied experimental conditions, considerable information has been obtained on the toxicity of CO, its direct effects on blood and other tissues, and the indications of these effects in the form of changes in organ function. The lethality of CO that results from extremely high concentrations is well known, but other effects of CO often are overlooked, especially in susceptible individuals. The health effects of low concentrations, such as levels found in ambient air, are far more subtle and considerably less threatening to the general public.

Perioperative factors influencing surgical morbidity: what the anesthesiologist needs to know.

S URGERY is accompanied by widespread changes in organ function. These functional changes are mediated by an alteration in the endocrine-metabolic milieu and activation of several biological cascade systems known as inflammatory mediators. These responses presumably evolved because they confer an advantage with respect to survival. In fact, it seems indisputable that when an individual organism acquires an enhanced ability to recover from an injury, the species is benefitted. However, the metabolic response can also be debilitaring and can lead to organ dysfunction. If amplified and prolonged, the body cell mass becomes eroded. Despite advances in anesthesia care and surgical techniques, major surgery is still beset with undesirable consequences amongst which the most important are infection, thrombo-embolic and cardio-respiratory complications, cerebral dysfunction, gastrointestinal paralysis, pain, fatigue and prolonged convalescence. Although postoperative morbidity can be related to some imperfections of surgery and anesthesia, complications do occur regardless of surgical skill and drug regimens. One could ask the simple question: why a successful operation is followed by an unsuccessful postoperative period? Clearly, the key pathogenic factor in postoperative morbidity is the surgical stress response with subsequent increased demands on organ function. The object of this review is to discuss postoperative pathophysiology and to propose a rationale for controlling the undesirable sequelae of surgical injury.

Multimodal Approach to Control Postoperative Pathophysiology and Rehabilitation

Major surgery is still associated with undesirable sequelae such as pain, cardiopulmonary, infective and thromboembolic complications, cerebral dysfunction, nausea and gastrointestinal paralysis, fatigue and prolonged convalescence. The key pathogenic factor in postoperative morbidity, excluding failures of surgical and anaesthetic technique, is the surgical stress response with subsequent increased demands on organ function. These changes in organ function are thought to be mediated by trauma-induced endocrine metabolic changes and activation of several biological cascade systems (cytokines, complement, arachidonic acid metabolites, nitric oxide, free oxygen radicals, etc). To understand postoperative morbidity it is therefore necessary to understand the pathophysiological role of the various components of the surgical stress response and to determine if modification of such responses may improve surgical outcome. While no single technique or drug regimen has been shown to eliminate postoperative morbidity and mortality, multimodal interventions may lead to a major reduction in the undesirable sequelae of surgical injury with improved recovery and reduction in postoperative morbidity and overall costs.

Pharmacokinetic variability in the adolescent: Implications of body size and organ function for dosage regimen design

Although there are convincing clinical studies demonstrating important pharmacokinetic differences between the adult and Pediatric patient, guidelines for adjusting the dosages of specific drugs are often based on empirical and limited data. Adult doses often provide the reference point for therapy in children with adjustment for body size. Both body weight and body surface area (BSA) are commonly used to adjust adult doses for pediatric patients but yield substantially different absolute doses. For the child age five years, the BSA-based dose will be more than 50 percent greater than the dose adjusted for body weight. The choice of weight or BSA is often arbitrary and may be an important confounding variable when evaluating drugs over wide ranges of age in pediatric patients or comparing two drugs for which doses are not adjusted in a similar manner. For example, comparative trials for HIV-infected pediatric patients are evaluating zidovudine dosed by BSA with zalcitabine dosed by body weight. Organ function changes with age in pediatric patients yet little information is available on the effects of maturation on hepatic or renal function and the consequences for drug disposition. The use of model substrates for organ function offers potential for elucidating organ function relative to maturation and, in particular, to those functional capacities associated with the onset of puberty and gender differentiation.

Response of man to endotoxin

Endotoxin, a cell wall component of Gram-negative bacteria, plays a central role in the pathogenesis of septic shock. By administering small doses of intravenous endotoxin to humans, a variety of acute inflammatory responses are induced which are qualitatively similar to those that occur during the early stages of septic shock. Within hours of the administration of intravenous endotoxin to human volunteers, changes occur in systemic hemodynamics, ventricular function, pulmonary gas exchange and permeability. In conjunction with these changes in organ function, a wide variety of inflammatory mediators are released which appear to contribute to these responses. These include the release of proinflammatory cytokines (e.g. tumor necrosis factor-α, IL-1β, IL-6, IL-8), activation of the fibrinolytic system, kallikreinkinin generation and phospholipase A2 release. Phagocytic leukocytes are primed for enhanced inflammatory responses following endotoxin administration. Counter-regulatory responses are initiated in parallel and may serve to limit some of the end-organ responses by the inflammatory mediators. This human model provides a unique opportunity to extend previous concepts of acute inflammation and to evaluate the earliest responses activated after exposure to an important bacterial component. Defining the pathways and responses initiated during acute human endotoxemia may allow a better understanding of host responses that are critical to the development of organ dysfunction and shock due to severe infections.