Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated.

Recent studies from our laboratory demonstrated that mucosal lymphoid tissue such as Peyer's patch cells and lamina propria (LP) B lymphocytes from mice shows evidence of increased apoptosis after sepsis that is associated with localized inflammation/activation. The mechanism for this is poorly understood. Endotoxin as well as Fas/Fas ligand (FasL) have been shown to augment lymphocyte apoptosis; however, their contribution to the increase of apoptosis in LP B-cells during sepsis is not known.

Linkage to medical services in the Drug Abuse Treatment Outcome Study.

Background: An episode of substance abuse treatment is an opportunity to link substance-abusing patients to medical care at a time when management of medical problems might stabilize recovery and long-term health. However, little is known about the ability of organizational linkage mechanisms to facilitate the delivery of medical care to this population.

Objectives: The goal of this study was to examine whether organizational linkage mechanisms facilitate medical service utilization in drug abuse treatment programs.

A 9-year, single-institution, retrospective review of death rate and prognostic factors in adult respiratory distress syndrome.

Objective: To evaluate, at a single institution, the adult respiratory distress syndrome (ARDS) death rate in critically ill ventilated surgical/trauma patients and to identify the factors predicting death in these patients.

Summary Background Data: The prognostic features affecting mortality at the onset of ARDS have not been clearly defined. Defining rare characteristics would be valuable because it would allow for better stratification of patients in clinical trials and more appropriate utilization of constrained resources in ICU environments.

Evolution of an immune suppressive macrophage phenotype as a product of P38 MAPK activation in polymicrobial sepsis.

Studies indicate that polymicrobial sepsis in humans and animals is characterized by a biphasic response, which is dominated early by proinflammation, but over time develops into a state of generalized anti-inflammation (depressed Th1 cell response and decreased macrophage (M0) capacity to release proinflammatory cytokines). However, with respect to the macrophage, it remains unknown what mechanism(s) controls this change. In this regard it is well documented that the p38 mitogen activated protein kinase pathway (MAPK) plays a central role in the regulation of Mphi functions.

Gut-derived norepinephrine plays a critical role in producing hepatocellular dysfunction during early sepsis.

Although plasma norepinephrine (NE) increases and hepatocellular function is depressed during early sepsis, it is unknown whether gut is a significant source of NE and, if so, whether gut-derived NE helps produce hepatocellular dysfunction. We subjected rats to sepsis by cecal ligation and puncture (CLP), and 2 h later (i.e.

Critical role of oxygen radicals in the initiation of hepatic depression after trauma hemorrhage.

Background: Although depression in hepatocellular function occurs early after trauma and severe hemorrhage and persists despite fluid resuscitation, it remains unknown whether reactive oxygen species (ROS) play any role in the initiation of hepatocellular depression and damage under those conditions. We hypothesized that administration of a ROS scavenger at the beginning of resuscitation will attenuate organ injury after severe shock.

Methods: Male Sprague-Dawley rats (275-325 g) underwent laparotomy (i.

Estradiol administration after trauma-hemorrhage improves cardiovascular and hepatocellular functions in male animals.

Objective: To determine whether female sex steroids have any salutary effects on the depressed cardiovascular and hepatocellular functions following trauma and hemorrhage in male animals.

Summary Background Data: Studies indicate that gender difference exists in the immune and cardiovascular responses to trauma-hemorrhage, and that male sex steroids appear to be responsible for producing immune and organ dysfunction, but it remains unknown if female sex steroids produce any salutary effects on the depressed cellular and organ functions in males following trauma and hemorrhage.

Method: Adult male Sprague-Dawley rats underwent a midline laparotomy (i.

Does early infusion of red blood cells after trauma and hemorrhage improve organ functions?

Objective: Early management of trauma victims includes control of bleeding and rapid restoration of intravascular volume. However, it remains controversial whether infusion of blood products is superior to crystalloids alone. Therefore, it was the aim of the present study to determine whether resuscitation with red blood cells plus lactated Ringer's solution (RL) is more effective than RL alone in improving the cardiovascular and hepatocellular functions after trauma and severe hemorrhage.

Testosterone receptor blockade after trauma and hemorrhage attenuates depressed adrenal function.

Although the testosterone receptor antagonist flutamide restores the depressed immune function in males after trauma and hemorrhage, it remains unknown whether this agent has any salutary effects on adrenal function. To study this, male rats underwent laparotomy and were bled to and maintained at a blood pressure of 40 mmHg until 40% of the shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated and flutamide (25 mg/kg body wt) was administered subcutaneously.

Androgen and estrogen receptors in splenic T lymphocytes: effects of flutamide and trauma-hemorrhage.

The endogenous sex steroids, testosterone and beta-estradiol, play a major role in inflammatory processes. They regulate several cytokine genes by interaction with their intracellular receptors that are, essentially, transcription factors. Because T-lymphocyte functions are altered following trauma-hemorrhage in male mice, we investigated whether (i) receptors for androgen (AR) and estrogen (ER) are present in splenic T lymphocytes, (ii) receptor expressions are altered following trauma-hemorrhage, and (iii) pretreatment of male mice with the AR antagonist, flutamide, alters receptor expressions and IL-6 release.

The aromatase inhibitor, 4-hydroxyandrostenedione, restores immune responses following trauma-hemorrhage in males and decreases mortality from subsequent sepsis.

Studies have shown that immune responses are depressed in male mice, but not in proestrus females after trauma-hemorrhage (TH), resulting in increased mortality from subsequent sepsis in male mice compared with female mice. These gender-specific alterations in immune function are believed to be due to differences in sex steroid levels. Aromatase is a key enzyme in the sex steroid biosynthesis.

L-arginine attenuates trauma-hemorrhage-induced liver injury.

Objectives: Liver injury is common after trauma-hemorrhage for which the underlying mechanism is not clear. Although administration of the essential amino acid L-arginine has been reported to restore the depressed cardiovascular functions and cell-mediated immune responses after trauma-hemorrhage, it remains unknown whether L-arginine protects against liver injury under those conditions.

Design: A prospective, controlled animal study.

Percutaneous injection of thrombin for the treatment of pseudoaneurysms after catheterization: an alternative to sonographically guided compression.

Objective: The purpose of our study was to determine the efficacy of percutaneous thrombin treatment for iatrogenic pseudoaneurysms of the femoral artery in comparison with sonographically guided compression repair.

Subjects And Methods: Twenty-three pseudoaneurysms occurring after catheterization were treated percutaneously with an initial injection of 1.0 mL of thrombin solution via a 22-gauge spinal needle under continuous sonographic guidance.

Immune depression in polymicrobial sepsis: the role of necrotic (injured) tissue and endotoxin.

Objective: Recent studies suggest immune dysfunction seen after the onset of polymicrobial sepsis, as produced by cecal ligation and puncture (CLP), is not caused by endotoxin (ETX) alone, but may be caused by the combined effect of the necrotic tissue (cecal ligation, [CL]) and other microbial components. Thus, the objective of this study was to assess the ability of necrotic tissue, in the presence or absence of low-dose endotoxin, to induce changes in the capacity of immune cells to produce proinflammatory or anti-inflammatory cytokines approximating those seen in CLP.

Design: Experimental, prospective study.

Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock.

Objectives: Although trauma and hemorrhage are associated with tissue hypoperfusion and hypoxemia, changes in oxygen delivery (DO2), oxygen consumption VO2), and oxygen extraction at the organ level in a small animal (such as the rat) model of trauma and hemorrhage have not been examined. Therefore, the objectives of this study were to determine whether blood flow, DO2, VO2, and oxygen extraction ratio in various organs are differentially altered after trauma-hemorrhagic shock and acute resuscitation in the rat.

Design: Prospective, randomized animal study.

Effect of gender and sex hormones on immune responses following shock.

Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions.

Insight into the mechanism by which estradiol improves organ functions after trauma-hemorrhage.

Background: Recent studies have indicated that female rodents with high levels of estradiol (proestrus) have better organ functions after trauma-hemorrhage than females with low estradiol levels (estrus) or male animals. However, the precise role of estrogens in maintaining organ function after hemorrhage remains unknown.

Methods: Adult female Sprague-Dawley rats were ovariectomized 14 days before the experiment to decrease circulating levels of estradiol.

Suppression of PMN apoptosis by hypoxia is dependent on Mcl-1 and MAPK activity.

Background: Hypoxia has been shown to delay the onset of neutrophil (polymorphonuclear leukocytes [PMNs]) apoptosis. With the use of antisense oligonucleotides, we have previously demonstrated that Mcl-1 is necessary for this effect. We wanted to further characterize the expression of Mcl-1 and examine signaling pathways required for the delay in apoptosis that is mediated by hypoxia.

IL-4-induced activation of the Stat6 pathway contributes to the suppression of cell-mediated immunity and death in sepsis.

Background: Although studies have shown that there is a marked depression in cell-mediated (T(H)(1)) immunity after the onset of sepsis, the mechanism by which this occurs remains unknown. In this regard, the T(H2) cytokine IL-4 is known to regulate T(H1) and T(H2) cell responsiveness primarily through the activation of the signal transducer and activation of transcription factor-6 (Stat6) pathway.

Methods: We hypothesized that IL-4 may contribute to the suppression of cell-mediated immunity and to death seen in sepsis and that IL-4 may be acting through the Stat6 pathway.

The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis.

The regulation of polymorphonuclear leukocyte (PMN) apoptosis can influence the duration of the inflammatory response. We have previously shown that PMN apoptosis is delayed by matrix adhesion and hypoxia; however, the mechanisms responsible for this delay are not well understood. Mcl-1, an antiapoptotic Bcl-2 family member, is present in neutrophils; therefore, we sought to characterize its localization and function as it relates to PMN apoptosis.

Insight into the mechanism by which metoclopramide improves immune functions after trauma-hemorrhage.

Although studies have shown that prolactin (Prl) and metoclopramide (Mcp) administration restores the depressed cell-mediated immune functions after hemorrhage, the underlying mechanism responsible for the immunostimulatory effects of Mcp remains unknown. We hypothesized that Mcp improves immune responses by upregulating the secretion of Prl. To test this hypothesis, male C3H/HeN mice were subjected to sham operation or laparotomy (i.

Relevance of the lesser occipital nerve in facial rejuvenation surgery.

Nerve injuries are possible during facial rejuvenation surgery. The great auricular nerve has been studied; however, little is known about the lesser occipital nerve and its relevance in facial rejuvenation surgery. To understand the importance of the lesser occipital nerve in a face lift procedure, the specific anatomy of the nerve was studied in the laboratory in 19 hemifaces, with additional nerve observations in the operating room.

The dissociation between upregulated endothelins and hemodynamic responses during polymicrobial sepsis.

Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Although studies have suggested that endothelins (ETs) contribute to the development of shock after a bolus injection of endotoxin, little is known about the role of ETs in the transition from the hyperdynamic phase to the hypodynamic phase of sepsis. To study this, male adult rats were subjected to sepsis by cecal ligation and puncture (CLP) followed by fluid resuscitation.

Is prostacyclin responsible for producing the hyperdynamic response during early sepsis?

Objective: Although polymicrobial sepsis is characterized by an early hyperdynamic phase (2-10 hrs after cecal ligation and puncture [CLP]), followed by a late hypodynamic phase (20 hrs after CLP), it remains unknown whether prostacyclin or prostaglandin I2 (PGI2) plays a significant role in modulating the hyperdynamic state during early sepsis. The aim of this study was to determine whether inhibition of PGI2 synthesis prevents the occurrence of the hyperdynamic response during early sepsis.

Design: Prospective, controlled animal study.

Septic mucosal intraepithelial lymphoid immune suppression: role for nitric oxide not interleukin-10 or transforming growth factor-beta.

Objective: Recent studies indicate that sepsis induces a marked depression in the splenocyte immune response (as illustrated by decreased interleukin [IL]-2 production, interferon [IFN]-gamma production, or both) in response to T-cell mitogen. However, it is not known whether a similar depression is evident in the phenotypically distinct, small intestine intraepithelial lymphocytes (IELs) or what regulates this process during sepsis. Because the maintenance of a competent mucosal immune response is thought to be central to the animal's ability to survive sepsis, we attempted to determine whether IEL's IL-2/IFN-gamma production is suppressed and what mediates this depression.