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Biomedical subjects

O D Rotstein

Publications and source records attributed to O D Rotstein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction.

OBJECTIVE: In normal pregnancy there is both a neutrophilia and a mild neutrophil activation. In preeclampsia both direct and indirect evidence supports further marked neutrophil activation. In the pathogenesis of preeclampsia peripheral blood neutrophils may play a vital role in communicating between the preeclamptic placenta and the maternal vascular endothelium and contribute to the endothelial cell dysfunction that characterizes the maternal syndrome of preeclampsia. Preeclampsia shares many elements with the systemic inflammatory response syndrome. Neutrophils, key effectors of the systemic inflammatory response syndrome, are associated with hepatic necrosis and adult respiratory distress syndrome, both of which most commonly kill women with preeclampsia. We hypothesized that delayed neutrophil apoptosis could explain (1) the neutrophilia of normal pregnancy and (2) the differential maternal responses to the shared placental abnormality of preeclampsia and normotensive intrauterine growth restriction. STUDY DESIGN: Neutrophils were isolated (dextran 500, Ficoll [Amersham Pharmacia Biotech AB, Uppsala, Sweden], and erythrocyte lysis) from (1) case patients with preeclampsia at </=34 weeks' gestation, (2) healthy pregnant control subjects, (3) case patients with normotensive intrauterine growth restriction at </=34 weeks' gestation, and (4) nonpregnant female control subjects. Apoptosis was determined after 18 hours of incubation (with or without endotoxin or anti-Fas monoclonal antibody) by deoxyribonucleic acid profile (propidium iodide study), annexin V binding, and CD16 expression. RESULTS: Compared with propidium iodide profile values in nonpregnant women (median, 25%; range, 14%-40%) neutrophil apoptosis was significantly delayed in normal pregnancy (median, 9.5%; range, 7.6%-15%) and normotensive pregnancy with intrauterine growth restriction (median, 11%; range. 9.3%-19%) and was further delayed in preeclampsia (median, 6.9%; range, 4.1%-8. 2%; P </=.005 vs normal pregnancy and normotensive intrauterine growth restriction). All neutrophils remained sensitive to endotoxin inhibition but were resistant to anti-Fas induction of apoptosis. Spontaneous neutrophil apoptosis decreased as gestational age increased (r (2) = 0.48). CONCLUSIONS: Impaired neutrophil apoptosis may explain the neutrophilia associated with normal pregnancy. In women with preeclampsia activated neutrophils remain in the circulation, perhaps contributing to the persistence of preeclampsia after delivery. Neutrophils appear to modulate the variation in maternal response between preeclampsia and normotensive intrauterine growth restriction.

Adult↗
PubMed1999

Hypertonicity prevents lipopolysaccharide-stimulated CD11b/CD18 expression in human neutrophils in vitro: role for p38 inhibition.

BACKGROUND: Neutrophil sequestration in the lungs plays an important role in the development of acute respiratory distress syndrome. We previously reported that hypertonic saline resuscitation attenuated lung injury after hemorrhagic shock and lipopolysaccharide (LPS) by abolishing neutrophil CD11b up-regulation. We investigated the mechanism underlying this effect. METHODS: Human neutrophils were exposed to LPS in the presence or absence of hypertonicity or SB203580 (p38 inhibitor). CD11b and CD14 were studied by immunofluorescence and p38 phosphorylation by immunoblotting. RESULTS: Hypertonicity had no effect on CD11b or CD14, caused a weak p38 phosphorylation, and completely prevented the LPS-induced p38 phosphorylation and CD11b up-regulation. p38 inhibition also abrogated CD11b up-regulation by LPS. CONCLUSION: MAPKp38 is important in CD11b regulation by LPS. The inhibitory effect of hypertonicity on the LPS-mediated effect may contribute to its protective anti-inflammatory effect observed in vivo. Transient hypertonicity might minimize organ injury in diseases characterized by neutrophil-mediated damage such as ARDS.

Blotting, Western↗
PubMed1999

Antioxidant modulation of skin inflammation: preventing inflammatory progression by inhibiting neutrophil influx.

OBJECTIVE: To test the hypothesis that antioxidants might affect local inflammation by impairing inflammatory cell influx. DESIGN: A laboratory study using a Swiss-Webster mouse model of local inflammation. SETTING: A university-affiliated hospital. METHODS: Intradermal injection of 30 micrograms of S. minnesota endotoxin (LPS) to Swiss-Webster mice initiates a local inflammatory reaction characterized by an early rise in vascular permeability and a later infux of neutrophils. Animals were pretreated intraperitoneally with either pyrrolidine dithiocarbamate (PDTC, 2 mmol/kg), which inhibits free radical generation, or dimethylthiourea (DMTU, 450 mg/kg), a free radical scavenger. MAIN OUTCOME MEASURES: Histologic findings of tissue samples taken at sites of injection; local changes in tissue vascular permeability (PI) determined by iodine-125 albumin injection before sacrifice; neutrophil accumulation quantified by tissue myeloperoxidase levels; tissue levels of the endothelial adhesion molecules intercellular adhesion molecule-1 protein (ICAM-1) and vascular cell adhesion molecule-1 protein (VCAM-1) assessed by immunohistochemistry and Western blot, respectively. RESULTS: Neither antioxidant had a significant effect on the early increase in PI, but both decreased the late rise in PI and reduced neutrophil influx. Both ICAM-1 and VCAM-1 were upregulated in response to LPS; however, only the increase in VCAM-1 was attenuated by antioxidant pretreatment. CONCLUSION: These data suggest that antioxidants disrupt the propagation phase of an inflammatory response possibly by altering neutrophil migration.

Animals↗
PubMed1999

Delayed treatment with diethyl maleate prevents E-selectin expression in human endothelial cells.

BACKGROUND: Polymorphonuclear leukocyte (PMN) infiltration is a significant contributor to tissue damage in many disease states and is known to occur through an orderly set of events. The endothelial cell adhesion molecule E-selectin is involved in the initial rolling of PMNs on the endothelium at sites of inflammation. We have previously shown that the glutathione depleting agent diethyl maleate (DEM) attenuates lung injury in a rodent model of intratracheal LPS stimulation. We hypothesized that DEM might attenuate E-selectin in LPS-treated human umbilical vein endothelial cells as a mechanism underlying this effect. Further, we investigated the role of delayed treatment with DEM on E-selectin expression. METHODS: Human umbilical vein endothelial cells were treated with DEM (100 to 400 mumol/L) before or after LPS stimulation (1 microgram/mL). Surface expression of E-selectin was examined using a cellular enzyme-linked immunosorbent assay. E-selectin mRNA transcripts were detected by Northern blot analysis. Nuclear factor-kappa B (NF-kappa B) activity was detected with gel shift assays. RESULTS: DEM significantly inhibited LPS-induced E-selectin surface expression and mRNA levels in a dose-dependent fashion, with complete inhibition at 250 mumol/L, without affecting cell viability. This inhibitory effect was seen even if DEM was added up to 60 minutes after LPS. DEM inhibited NF-kappa B nuclear translocation in a manner that mirrored protein and mRNA levels. CONCLUSIONS: Delayed treatment with DEM attenuates NF-kappa B nuclear translocation and E-selectin expression in human umbilical vein endothelial cells up to 60 minutes after the onset of LPS stimulation. Thus, DEM may represent an effective intervention for PMN-mediated organ injury even when given after an inflammatory insult.

Cells, Cultured↗
PubMed1999

Typhlitis.

OBJECTIVE: To provide an overview of the pathophysiological features and management of the clinical entity typhlitis. DATA SOURCES AND STUDY SELECTION: The data presented are derived from a review of the English-language literature on typhlitis. The majority of papers analysed were small clinical series. DATA EXTRACTION AND SYNTHESIS: Data derived from the literature review were collated. The major finding was that typhlitis comprises a number of different diseases characterized by the presence of right lower quadrant pain, an immunocompromised host and altered function of the mucosal barrier of the right colon. CONCLUSIONS: Typhlitis should be suspected in any immunocompromised patient presenting with right lower quadrant pain with compatible radiographic findings. Most patients can be treated conservatively with intravenously administered fluids and antibiotics, although surgery may be necessary if complications arise.

Enterocolitis↗
PubMed1998

Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock.

Hypertonic resuscitation fluids are known to be effective in restoring circulating volume in the hypovolemic trauma patient. Previous studies have suggested that hypertonicity might exert effects on immune cells leading to an altered host response. The present studies evaluated the effect of hypertonic resuscitation on the development of lung injury in a hemorrhagic shock model in which antecedent shock primes for increased lung neutrophil sequestration in response to intratracheal LPS. Resuscitation with hypertonic saline significantly reduced albumin leak, bronchoalveolar lavage fluid neutrophil counts, and the degree of histopathologic injury compared with resuscitation with Ringer's lactate. Both in vivo and in vitro data suggest that this beneficial effect may be related to altered adhesion molecule expression by the neutrophil. Specifically, hypertonicity induced shedding of L-selectin and prevented LPS-stimulated expression and activation of CD11b, both of which might contribute to reduced sequestration in the lung. Impaired up-regulation of lung ICAM-1 may have also participated, although ex vivo studies suggest that alterations in neutrophils were sufficient to account for the effect. Lung cytokine-induced neutrophil chemoattractant did not differ between animals resuscitated with hypertonic saline vs Ringer's lactate. Considered together, these studies demonstrate a possible novel approach to inhibiting organ injury in disease processes characterized by neutrophil-mediated damage.

Adjuvants, Immunologic↗
PubMed1998

Murine hepatitis virus strain 3 induces the macrophage prothrombinase fgl-2 through p38 mitogen-activated protein kinase activation.

The clinical syndrome of acute liver failure produced by fulminant viral hepatitis can be reproduced in mice by infection with murine hepatitis virus strain 3 (MHV-3). Although it is clear that MHV-3-induced hepatitis depends upon macrophage activation and the expression of a specific prothrombinase, fgl-2, the signaling pathways involved in virally stimulated cell activation are unclear. Since we had previously found that MHV-3 induces the tyrosine phosphorylation of cellular proteins, we investigated the roles of the mitogen-activated protein kinase (MAPK) proteins. In a series of Western blots, immunoprecipitation and in vitro kinase assay studies, we found that both the extracellular signal-related kinase (ERK) and p38 MAPK proteins are tyrosine-phosphorylated and activated following exposure of murine peritoneal exudative macrophages (PEM) to MHV-3. Although p38 phosphorylation and activity are induced soon after MHV-3 exposure, peaking by 1-5 min, ERK phosphorylation and activity increase more gradually, peaking at 20-30 min and gradually fading thereafter. Interestingly, whereas selective p38 inhibition with SB203580 (1-20 microM) abolished the virally stimulated induction of fgl-2 mRNA, protein, and functional activity, selective ERK inhibition with PD98059 (1-50 microM) limited fgl-2 functional activity but had little to no effect on fgl-2 mRNA or protein levels. Moreover, whereas inhibition of ERK had no effect on p38 activity, p38 inhibition consistently increased MHV-3-induced ERK activity. To ensure that these pathways were relevant in vivo, MHV-3 was injected intraperitoneally, and peritoneal exudative macrophages were collected. Again, MHV-3 exposure led to increased p38 and ERK tyrosine phosphorylation. These data argue that MHV-3 induces tightly interconnected ERK and p38 MAPK cascades in the macrophage both in vitro and in vivo. Although the ERK and p38 MAPK proteins have discordant effects at the level of fgl-2 expression, both converge at the level of its activity, suggesting that targeted MAPK inhibition may ultimately be useful in the modulation of viral hepatitis.

Animals↗
PubMed1998

v-SNARE-dependent secretion is required for phagocytosis.

Phagosomes are generally believed to form by gradual apposition of the plasma membrane of leukocytes onto the surface of invading microorganisms. The internalization of the encapsulated particle is therefore predicted to reduce the surface area of the phagocyte. Contrary to this prediction, we observed that phagocytosis is associated with a net increase in cell surface area, suggesting the concomitant occurrence of exocytosis. Selective cleavage of components of the secretory machinery by microinjection or transfection of bacterial neurotoxins induced a pronounced inhibition of phagocytosis. These observations indicate that vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis of endomembranes is essential for optimal completion of particle internalization during phagocytosis.

Animals↗
PubMed1998

Host resistance to intracellular infection: mutation of natural resistance-associated macrophage protein 1 (Nramp1) impairs phagosomal acidification.

The mechanisms underlying the survival of intracellular parasites such as mycobacteria in host macrophages remain poorly understood. In mice, mutations at the Nramp1 gene (for natural resistance-associated macrophage protein), cause susceptibility to mycobacterial infections. Nramp1 encodes an integral membrane protein that is recruited to the phagosome membrane in infected macrophages. In this study, we used microfluorescence ratio imaging of macrophages from wild-type and Nramp1 mutant mice to analyze the effect of loss of Nramp1 function on the properties of phagosomes containing inert particles or live mycobacteria. The pH of phagosomes containing live Mycobacterium bovis was significantly more acidic in Nramp1- expressing macrophages than in mutant cells (pH 5.5 +/- 0.06 versus pH 6.6 +/- 0.05, respectively; P <0.005). The enhanced acidification could not be accounted for by differences in proton consumption during dismutation of superoxide, phagosomal buffering power, counterion conductance, or in the rate of proton "leak", as these were found to be comparable in wild-type and Nramp1-deficient macrophages. Rather, after ingestion of live mycobacteria, Nramp1-expressing cells exhibited increased concanamycin-sensitive H+ pumping across the phagosomal membrane. This was associated with an enhanced ability of phagosomes to fuse with vacuolar-type ATPase-containing late endosomes and/or lysosomes. This effect was restricted to live M. bovis and was not seen in phagosomes containing dead M. bovis or latex beads. These data support the notion that Nramp1 affects intracellular mycobacterial replication by modulating phagosomal pH, suggesting that Nramp1 plays a central role in this process.

Animals↗
PubMed1998

The IL-1 beta-converting enzyme (caspase-1) inhibits apoptosis of inflammatory neutrophils through activation of IL-1 beta.

IL-1 beta-converting enzyme (ICE), also known as caspase-1, subserves two dichotomous biologic roles. It processes newly synthesized pro-IL-1 beta to yield the active cytokine and, as the human homologue of the Caenorhabditis elegans gene product, ced-3, it also induces cellular apoptosis through the cleavage of key intracellular structural and regulatory proteins and through the catalytic activation of other caspase family members. We show here that two different proinflammatory stimuli, LPS and granulocyte-macrophage-CSF, up-regulate the expression of both ICE and IL-1 beta in human polymorphonuclear neutrophils, and that the ICE-dependent cleavage of pro-IL-1 beta results in delayed expression of the constitutive cell death program. The apoptotic delay can be blocked by inhibiting tyrosine kinases or NF-kappa B activation and by inhibiting protein synthesis. Since an antisense oligonucleotide for IL-1 beta, a blocking Ab to IL-1 beta, and preincubation with the IL-1R antagonist all prevent the delay in apoptosis, we conclude that IL-1 beta acts in an autocrine manner to inhibit granulocyte programmed cell death. We conclude that caspase-1 (ICE) subserves both pro- and antiapoptotic roles; the latter role is evident during inflammation as an inhibition of spontaneous neutrophil apoptosis through the processing of IL-1 beta. The ICE-dependent activation of IL-1 beta may represent a common autocrine pathway for the divergent stimuli that inhibit the constitutive expression of neutrophil programmed cell death during inflammation.

Apoptosis↗
PubMed1998

Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil chemoattractant in the lung: role in pulmonary inflammation following lipopolysaccharide.

Recent studies have suggested that hemorrhagic shock followed by resuscitation renders patients more susceptible to lung injury by priming for an exaggerated response to a second stimulus, the so-called "two-hit" hypothesis. We investigated the role of C-X-C chemokines in mediating the augmented lung inflammation in response to LPS following resuscitated shock. In a rodent model, animals exposed to antecedent shock exhibited enhanced lung neutrophil sequestration and transpulmonary albumin flux in response to intratracheal LPS. This effect correlated with an exaggerated expression of cytokine-induced neutrophil chemoattractant (CINC) protein and mRNA, but not macrophage-inflammatory protein 2. Strategies designed to inhibit CINC, both anti-CINC Ab and supplementation with the antioxidant N-acetyl-cysteine, prevented the enhanced neutrophil sequestration, suggesting that CINC played a central role in the enhanced leukocyte accumulation following shock plus LPS treatment. Shock alone increased lung nuclear factor-kappaB expression and augmented the response to LPS. Prevention of this effect by N-acetylcysteine supplementation of the resuscitation fluid implicates a role for oxidant stress in the priming for lung inflammation following shock. Finally, alveolar macrophages recovered from shock-resuscitated animals released more CINC protein in vitro in response to LPS than macrophages from sham animals. Considered together, these findings show that augmented release of CINC, in part from primed alveolar macrophages, contributes significantly to the enhanced lung leukosequestration and transpulmonary albumin flux in response to LPS following resuscitated shock.

Acetylcysteine↗
PubMed1998

Thiol-mediated regulation of ICAM-1 expression in endotoxin-induced acute lung injury.

The intracellular redox state regulates several aspects of cell function, suggesting that strategies directed toward altering the cellular redox state may modulate cell activation in inflammatory states. As the most abundant intracellular thiol, glutathione plays a critical role as an intracellular redox buffer. Using diethylmaleate (DEM) as a glutathione-depleting agent, we evaluated the effects of GSH depletion in a rodent model of polymorphonuclear neutrophil (PMN)-dependent acute lung injury. Rats received 500 microg of LPS by intratracheal challenge, inducing a 5.5-fold increase in lung permeability and sixfold increase in lung PMN content. Pretreatment with DEM prevented the LPS-induced increase in lung PMN influx and lung permeability. Northern analysis and immunohistochemical studies suggest that this effect may be mediated by preventing up-regulation of lung ICAM-1 mRNA and protein expression. This effect is specific to ICAM-1, because lung cytokine-induced neutrophil chemoattractant and TNF-alpha mRNA levels are unaffected. This finding is not unique to the lung, because a similar effect on PMN influx was recapitulated in a rodent model of chemical peritonitis. Further, in vitro studies demonstrated that pretreatment of HUVEC monolayers with DEM prevented both ICAM-1 up-regulation and PMN transendothelial migration. These data indicate the presence of a thiol-sensitive mechanism for modulating ICAM-1 gene expression and suggest a potential novel therapeutic strategy for diseases characterized by PMN-mediated tissue injury.

Animals↗
PubMed1998

Bioavailability of oral ciprofloxacin in early postsurgical patients.

OBJECTIVE: To evaluate the absorption of oral ciprofloxacin within 24 hours of laparotomy for major elective surgery or peritonitis. DESIGN: In this prospective trial, patients were given a 750-mg oral close the morning after major elective surgery (n=15) or surgery for peritonitis (n=7). Healthy volunteers served as controls (n=9). Serial urine and blood samples were drawn during the subsequent 12 hours, and pharmacokinetic measures were determined by standard high-performance liquid chromatography assay procedures. SETTING: Multicenter, university-affiliated hospitals. MAIN OUTCOME MEASURES: Drug absorption as determined by area under the concentration time curve, maximum concentration, and time to maximum concentration. RESULTS: Oral bioavailability was reduced in elective surgery and peritonitis patients compared with controls. Among the 15 elective surgery patients, 27% (4/15) showed no absorption. The remaining 73% (11/15) had an area under the curve comparable with that of controls (8.3+/-1.6 (mg/[L x h]). Among all patients, those who showed drug absorption vs those who showed no absorption did not differ with respect to malignant neoplasm, case type, age, or biochemistry. However, patients showing no absorption were significantly heavier than patients showing absorption (patients showing absorption, 15%+/-3% over ideal body weight vs patients showing no absorption, 29%+/-6% over ideal body weight; P<.05). When elective surgery patients were stratified by presence or absence of obesity (25% above ideal body weight), mean area under the curve in nonobese patients was 9.80+/-2.37 vs 0.91+/-0.56 (mg/(L x h) in obese patients (P<.05). CONCLUSIONS: Oral bioavailability was reduced for peritonitis surgery patients on the first day postoperatively, and for obese elective surgery patients. To achieve adequate serum levels requires continuation of intravenous antibiotics in patients with peritonitis, and adjustment of oral dosage in obese patients in the early period after elective surgery.

Administration, Oral↗
PubMed1998

MAP-kinase dependent induction of monocytic procoagulant activity by beta2-integrins.

beta2-Integrin adhesion molecules play crucial roles in monocyte transmigration and adherence to the inflamed extracellular matrix. While integrin engagement contributes to inflammatory cell activation, little is known about the precise signaling pathways that are important to integrin-dependent monocyte activation. We examined the role of tyrosine phosphorylation and extracellular-signal regulated kinase (ERK) activity in beta2-integrin signaling in monocytes. Cross-linking of the LFA-1 (CD11a/CD18) and MAC-1 (CD11b/CD18) integrins on the surface of THP-1 monocytic cells induced the accumulation of tyrosine phosphoproteins. As part of this signal both ERK-1 and ERK-2 are tyrosine phosphorylated. In vitro kinase assays documented an increase in ERK-2 activity following both LFA-1 and MAC-1 cross-linking. beta2-Integrin cross-linking also led to a marked increase in 4-h procoagulant activity (PCA) in THP-1 cells and purified human monocytes. Inhibition of tyrosine phosphorylation by genistein (10 microg/ml), or selective ERK inhibition with PD98059 (10 microM), was able to block the integrin-dependent induction of PCA in both THP-1 cells and human monocytes. Thus, beta2 integrin signaling in monocytic cells can flow through the tyrosine phosphorylation and activation of the ERK mitogen activated protein kinases, which is essential for the subsequent expression of tissue factor. These results suggest that the ERK proteins likely function to integrate various adhesion-dependent signals during the process of monocyte transmigration.

Blood Coagulation Factors↗
PubMed1998

The glutathione depleting agent diethylmaleate prolongs renal allograft survival.

INTRODUCTION: Intercellular adhesion molecule 1 (ICAM-1) plays an important role in mediating allograft rejection through its role in cellular trafficking and as an important costimulatory signal mediating T cell activation. We have previously reported that systemic administration of the glutathione (GSH) depleting agent diethylmaleate (DEM) prevents upregulation of ICAM-1 in various inflammatory models, suggesting that this agent may offer benefit in preventing allograft rejection. Thus we evaluated the effects of DEM in a murine model of renal transplantation. METHODS: Kidneys from C57BL/6 mice were transplanted into MHC incompatible C3H mice. Donors were treated with DEM 1 h prior to sacrifice, whereas recipients received DEM 1 h following transplantation. Animals were followed until the time of death. In separate studies, renal ICAM-1 mRNA expression was evaluated by polymerase chain reaction and the CD4(+) T cell cytokine profile evaluated in a mixed lymphocyte reaction using C3H responder splenocytes and C57BL/6 stimulator cells. RESULTS: Pretreatment with DEM increased survival from 18.9 +/- 3.6 to 30.6 +/- 10 days (P < 0.05). This increase in survival was associated with a reduction in renal ICAM-1 mRNA expression. Mixed lymphocyte cultures derived from animals pretreated with DEM demonstrated a reduction in the Th1 cytokines IFN-gamma and IL-2 and an increase in the Th2 cytokines IL-4 and IL-10. CONCLUSION: Administration of DEM with consequent systemic GSH depletion significantly reduces allograft ICAM-1 expression and prolongs graft survival. Although speculative, a shift from a Th1 to a Th2 cytokine response raises the possibility that tolerance induction plays a role in prolonged allograft survival.

Animals↗
PubMed1998

Tertiary peritonitis: clinical features of a complex nosocomial infection.

The objective of this study was to define risk factors for and the clinical course of recurrent or tertiary peritonitis. Intensive supportive care of patients with life-threatening intraabdominal infections has led to the emergence of a new clinical syndrome, tertiary peritonitis, defined as the persistence or recurrence of intraabdominal infection following apparently adequate therapy of primary or secondary peritonitis. We undertook a retrospective study of 59 patients admitted with intraabdominal infection to a surgical intensive care unit (ICU). Tertiary peritonitis developed in 74% (44/59) of patients. Despite comparable premorbid health status, source of peritonitis, and admission APACHE II scores, patients with tertiary peritonitis had a significantly longer ICU stay (21.8 +/- 14.9 vs. 8.5 +/- 7.9 days), more advanced organ dysfunction reflected in higher organ dysfunction scores (13.3 +/- 5.1 vs. 7.7 +/- 3.3), and higher ICU mortality (64% vs. 33%) than patients with uncomplicated secondary peritonitis. The most common infecting organisms in patients with tertiary peritonitis were Enterococcus, Candida, Staphylococcus epidermidis, and Enterobacter. Infectious foci were rarely amenable to percutaneous drainage and were found to be poorly localized at laparotomy. Recurrent, or tertiary, peritonitis is a common complication of intraabdominal infection in patients admitted to an ICU. It differs from uncomplicated secondary peritonitis in its microbial flora and lack of response to appropriate surgical and antibiotic therapy. Like nosocomial pneumonia in the critically ill patient, the syndrome appears to be more a reflection than a cause of adverse outcome.

Adult↗
PubMed1998

Role of the coagulation system in the local and systemic inflammatory response.

Activation of the coagulation cascade during the inflammatory response is an essential component of the host response to infection. Coagulation represents a double-edged sword. Necessary for hemostasis and the acute containment of an infective focus, it also amplifies the inflammatory response, decreases bacterial clearance, and in the critically ill patient contributes to end-organ damage and death. Evidence for these concepts is found in the fact that critically ill and septic patients consistently demonstrate marked abnormalities in their biochemical indices of coagulation. Moreover, there is excellent experimental evidence to suggest that replacement or inhibition of individual coagulation factors, either consumed or up-regulated during the inflammatory response, can attenuate both local and systemic injury and protect animals from otherwise fatal outcomes. Based on these facts, novel therapeutic approaches to the treatment of the systemic response to infection have been developed and tested in intensive care settings. Although promising results have been obtained, much work remains to be done in defining exactly which coagulation factors (or combination of factors) should be inhibited or replaced during treatment of the septic, critically ill patient. The experimental and clinical evidence linking the coagulation cascade to local and systemic inflammation is reviewed, and the status of the clinical trials performed to date is overviewed.

Animals↗