Transfus Med Rev, 1995 Jul, 9(3), 251 - 9 Blood component and immunotherapy in neonatal sepsis; Sweetman RW et al.; The future role of IVIG remains unclear . Many, but not all, studies indicate efficacy in the prevention of late-onset disease in premature infants . The role of type-specific IVIG is evolving and may hold promise for both prevention and treatment of neonatal sepsis . Granulocyte transfusions, as adjuvant therapy in neonatal sepsis, seem to be beneficial . However, the difficulty and expense of collection, as well as the advent of colony-stimulating factors, have shifted the focus away from their routine use . Colony-stimulating factors present varied and exciting potential uses, including modulating neonatal hematopoiesis . Current studies are primarily aimed at understanding their effects on neonatal hematopoiesis . Future studies will need to expand on this knowledge and examine what effects they have on treating or preventing neonatal sepsis. Thromb Res, 1995 Jul 1, 79(1), 83 - 93 Activation of the protein C pathway in acute sepsis; Alcaraz A et al.; To obtain quantitative information on the in vivo activation of the protein C system during the acute phase of sepsis, several components of the protein C pathway were studied in 18 patients . Blood samples were obtained one day after diagnosis (day 1) and, in 11 patients, also on the fourth and tenth days after diagnosis (days 4 and 10) . On day 1, patients showed laboratory signs of haemostatic alterations such as positive fibrinogen/fibrin degradation products, and increased thrombin:antithrombin-III (TAT) complex levels . Compared with the control group, patients on day 1 had significantly decreased (p < 0.001) antigenic protein C (69 +/- 28%) and protein C inhibitor (PCI) (33 +/- 22%) whereas a significant increase in the levels of activated protein C (APC) complexed with alpha 1-antitrypsin (alpha 1AT) (APC:alpha 1AT, 26 +/- 15 ng/mL) and APC:PCI complex (3.0 +/- 2.0 ng/mL), and in the level of plasma kallikrein (KK) complexes with PCI (KK:PCI) (31 +/- 22 ng/mL) was observed . There was a positive correlation between APC:alpha 1AT and TAT complex levels (r = 0.597, p = 0.009) . In the follow-up a trend toward normal values in antigenic protein C and PCI, and in APC:PCI and KK:PCI complex levels was found . However, PCI remained significantly decreased compared to normal values . C4b-binding protein, alpha 1AT, and TAT and APC:alpha 1AT complexes did not show any significant variations during the course of the disease, suggesting the contribution of the inflammatory and haemostatic responses, in spite of the good recovery of the patients . This study shows that in the course of sepsis, patients experience a generalized activation of the protein C pathway which was more prominent on day 1, resulting in the consumption of protein C and PCI and in the increase of APC:inhibitor complexes . Moreover, these data provide further evidence that KK:PCI circulating complexes occur in vivo. J Pediatr Surg, 1995 Jul, 30(7), 959 - 65; discussion 966 Weanling and adult rats differ in fatty acid and carnitine metabolism during sepsis; Linz DN et al.; Increased oxidation of fat is an important host response to sepsis, and carnitine is essential for long-chain fatty acid oxidation . Because neonates have low levels of carnitine, their ability to respond to a septic insult may be impaired . The purpose of this study was to compare fatty acid and carnitine metabolism in septic weanling (60 to 85 g) and septic adult (285 to 310 g) rats . Sepsis was induced in weanling and adult male Sprague-Dawley rats by cecal ligation and puncture (CLP) . The rats were killed 16 hours after CLP or sham operation, and serum glucose, lactate, beta-hydroxybutyrate, fatty acid, carnitine, liver fatty acid, and tissue carnitine levels were measured . The data suggest that during sepsis weanling rats may be more dependent on fatty acid oxidation than adult rats are, as evidenced by their elevated serum fatty acid and acylcarnitine levels, and relative hypoglycemia and hyperketonemia . In addition, although total serum carnitine levels were increased in both adult and weanling septic rats, tissue carnitine levels of weanling rats became significantly depleted during sepsis, unlike in adult rats . This study supports further investigation regarding the role of exogenous carnitine in newborn sepsis. Dtsch Med Wochenschr, 1995 Jun 23, 120(25-26), 912 - 6 {Fatal Aspergillus sepsis following orthotopic heart transplantation}; Tiroke A et al.; In a 64-year-old man heart transplantation had been performed for ischaemic heart disease . 7 months later severe vascular disease in the transplant necessitated a second transplantation . Both procedures had been performed under immunosuppression (cyclosporine, azathioprine, prednisolone, antithymocyte globulin), with a subsequent prednisolone maintenance dose of 10 mg daily . At first there were no complications, but 31 days after the re-transplantation atrial flutter developed . Although this was quickly terminated by drugs, circulatory failure set in . Because of signs of infection (white blood cell count 29,800/microliters, 17% stab cells, C-reactive protein 24 mg/l) broad-spectrum antibiotics were administered, but without response . As a trial anti-rejection treatment was started (prednisolone 250 mg daily: antithymocyte globulin 100 mg daily for 4 days) . When cytomegalovirus (CMV) infection was demonstrated, ganciclovir and CMV hyperimmunoglobulin were administered and slow improvement was noted . The finding of Aspergillus in tracheal secretion was interpreted as apathogenic colonization . The patient died from cardiorespiratory failure 57 days after the second transplantation . Autopsy revealed Aspergillus sepsis. Lijec Vjesn, 1995 Jun, 117 Suppl 2, 8 - 11 {Immunotherapy of sepsis and septic shock}; Ivanovic D et al.; An extraordinary advance in basic sciences and technology did not reduce high lethality rate of the septic shock patients . The lethality rate of those patients was and still is around 50% . A new knowledge about a role of an inflammatory response on the infection in the later fatal course of the septic patients, led to the new approach in the treatment . A trial to block an endotoxin, cytokines, especially TNF and IL-1, as well as some other substances, in experimental models of sepsis, in spite of inconsistent results, is promising . A clinical experiences are disappointing, at first because of our still poor knowledge about various cytokines cascade, feedback mechanisms, cellular protective mechanisms, etc . The new chapter on the treatment of that highly lethal syndrome is open, though a final achievement of that approach is not clear till now. Lijec Vjesn, 1995 Jun, 117 Suppl 2, 76 - 7 {Sepsis in surgery patients}; Zanic-Matanic D et al.; The aim of the study was to determine therapeutic possibilities in surgical patients with sepsis following gunshot wounds of the abdomen and lower extremities . Thirty patients who underwent repeated surgical procedures in general or peridural anesthesia were analyzed . Eleven patients developed ARDS, of which 7 also had acute renal insufficiency and required hemodialysis . Mechanical ventilatory support and PEEP therapy were instituted . In 4 cases, alprostidil at a dosage of 0.1 microgram/kg body weight/min over 2 days was given . Empirical use of antibiotics was at the beginning of the therapy carried out by penicillin, gentamicin and metronidazole and later according to the antibiogram . One patient presented with spinal meningitis after the insertion of peridural catheter. J Clin Endocrinol Metab, 1995 Jun, 80(6), 1799 - 803 Differential adaptation of glucocorticoid sensitivity of peripheral blood mononuclear leukocytes in patients with sepsis or septic shock; Molijn GJ et al.; In view of the immunosuppressive action of glucocorticoids (GCs), the activation of the hypothalamo-pituitary-adrenal axis in patients with sepsis or septic shock is paradoxical . At the same time, administration of GCs to these patients is not clearly beneficial . We investigated the role of GCs in severe illness by measuring the sensitivity of peripheral blood mononuclear leukocytes to GCs in a mitogen-stimulated lymphocyte proliferation assay . In addition, we studied the role of interleukin-2 and several other cytokines in this system . Cells from patients with sepsis or septic shock (n = 15) were more sensitive to the antiproliferative action of GCs than were cells from normal controls (IC50 6.7 +/- 2.1 nmol/L for patients vs . 19.5 +/- 2.5 nmol/L for controls; P < 0.01) . This increased sensitivity of the peripheral mononuclear cells to dexamethasone during the period of sepsis normalized during the ensuing period of clinical recovery of these patients . Dexamethasone inhibited the production of interleukin-2 in the mitogen-stimulated cells . Addition of interleukin-2 antagonized the suppressive effects of dexamethasone in a dose-dependent manner, both in cells from controls and in cells from patients with sepsis . To a lesser extent, the combination of interleukin-1, interleukin-6, and tumor necrosis factor-alpha also counteracted the effects of dexamethasone . In conclusion, our results suggest that not only the activity of the hypothalamo-pituitary-adrenal axis but also the sensitivity to GCs is regulated during sepsis and septic shock . Generally there is an increased sensitivity to GCs, which might help to protect the organism as a whole through supportive effects on metabolism and vasculature . This hypersensitivity is counteracted, possibly at the site of inflammation, by high local concentrations of cytokines . This would enable an adequate local response of the immune system in the presence of elevated cortisol levels . In view of the increased sensitivity of peripheral leukocytes to GCs, treatment of these patients with high doses of GCs may not be beneficial or may even be harmful. Crit Care Med, 1995 Jun, 23(6), 1080 - 9 Glycosylated recombinant human tumor necrosis factor binding protein-1 reduces mortality, shock, and production of tumor necrosis factor in rabbit Escherichia coli sepsis; Porat R et al.; OBJECTIVE: To examine the effect of glycosylated recombinant human tumor necrosis factor binding protein-1 (r-hTNF binding protein-1), the extracellular domain of the tumor necrosis factor receptor p55 produced in mammalian cells, in a rabbit model of circulatory shock due to Escherichia coli . DESIGN: Prospective, randomized, controlled trial . SETTING: University hospital research laboratory . SUBJECTS: Eighteen female, New Zealand white rabbits . INTERVENTIONS: Anesthetized rabbits, infused with E . coli (10(9) organisms/kg), were pretreated with either r-hTNF binding protein-1 or saline . Mean arterial pressure, central venous pressure, cardiac output, and heart rate were recorded every 20 mins for 1 hr before, and for 4 hrs after, the infusion of E . coli . Blood samples were obtained at 1-hr intervals for platelet count and white blood cell count, r-hTNF binding protein-1, and tumor necrosis factor (TNF) measurements . MEASUREMENTS AND MAIN RESULTS: Administration of r-hTNF binding protein-1 resulted in improvement of mean arterial pressure, cardiac output, and systemic vascular resistance, as compared with the vehicle-treated group (p < .05) . Treatment with r-hTNF binding protein-1 was associated with 100% survival, as compared with 55.6% of the saline-treated rabbits (p < .05) . Approximately 85% of r-hTNF binding protein-1 was cleared from the circulation 1 hr after the bolus injection (from 171 +/- 27 micrograms/mL at time = 0, to 27 +/- 4 micrograms/mL at 60 mins, decreasing to 6 +/- 2 micrograms/mL for the next 3 hrs) . The r-hTNF binding protein-1-treated rabbits had lower serum TNF bioactivity during the first 2 hrs (p < .01) . The decreased bioactivity of TNF was confirmed by a specific radioimmunoassay for rabbit TNF . However, at 4 hrs, the vehicle-treated rabbits had lower serum bioactive TNF concentrations (p < .05) . The decrease in TNF concentrations in the r-hTNF binding protein-1-treated rabbits resulted from decreased production and, in part, from carry-over of r-hTNF binding protein-1 into the bioassay . CONCLUSIONS: Treatment with r-hTNF binding protein-1 improved hemodynamic variables and survival of E . coli-challenged rabbits . Administration of r-hTNF binding protein-1 suppressed bioactivity of TNF in the circulation of these rabbits, and the production of TNF as well. J Infect Dis, 1995 Jun, 171(6), 1522 - 7 Thrombomodulin release in baboon sepsis: its dependence on the dose of Escherichia coli and the presence of tumor necrosis factor; Redl H et al.; This study was designed to test whether thrombomodulin is shed in septic baboons and whether shedding is blocked by antibody to tumor necrosis factor (anti-TNF) . Live Escherichia coli were injected intravenously into 24 baboons according to one of the following regimens: 5 x 10(8) or 2 x 10(9) cfu/kg (n = 6/8), 2 x 10(9) cfu/kg with placebo (n = 5), or pretreatment with 1 mg/kg anti-TNF 2 h before E . coli injection (n = 5) . E . coli administration resulted in a significant release of thrombomodulin in a dose-dependent manner; however, thrombomodulin release was significantly attenuated (180 to 40 ng/mL) by anti-TNF pretreatment . This is parallel to the reduction of neutrophil activation (elastase) . These results provide evidence for an E . coli dose-related and TNF-dependent thrombomodulin release into the plasma of septic baboons and suggest a possible role of anti-TNF in protection of the endothelium. Clin Chem, 1995 Jun, 41(6 Pt 1), 867 - 71 Prognostic role of antioxidant enzymes in sepsis: preliminary assessment; Warner A et al.; The prognostic potential of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was evaluated in sepsis . Enzyme concentrations were determined in samples obtained from septic patients at time of diagnosis . Statistically significant increases in activities of total plasma SOD (P < 0.003, n = 32), erythrocyte (RBC) SOD (P < 0.007, n = 16), plasma CAT (P < 0.0001, n = 32), and RBC CAT (P < 0.005, n = 16) were found in septic patients when compared with healthy adult controls (n = 7) . Further, within the group of septic patients, statistically significant differences were found for total plasma SOD (P < 0.05) and plasma CAT (P < 0.009) (but not for RBC determinations) when survivors (n = 15) were compared with nonsurvivors (n = 17) . No significant differences were found for either plasma or RBC enzyme concentrations when patients who developed adult respiratory distress syndrome were compared with those who did not . The most striking finding was that plasma total SOD values of > 10 kU/L were found in 7 of 21 (30%) patients who did not survive their sepsis and that these values did not overlap with any surviving patients or controls . However, while high total plasma SOD activity appears to have some potential as a prognostic indicator, lower values (0.0-8.8 kU/L) do not . For plasma CAT, despite finding statistically significant differences between survivors and nonsurvivors, the substantial overlap in the values obtained for the two groups limits the practical prognostic potential of this enzyme. Clin Perinatol, 1995 Jun, 22(2), 519 - 36 Inflammatory mediators and neonatal sepsis . Rarely has so little been known by so many about so much; Meadow W et al.; Many questions remain unanswered (and probably many more remain unasked) about neonatal sepsis . In addition, many mediators of inflammation have been implicated in neonatal sepsis at one time or another . The goal of this article is to put together what the authors view as some of the more important outstanding questions with what is known about some of the more important mediators . We address four questions specifically: (1) Why is neonatal sepsis different from all other (adult) sepsis? (2) 41Is control of pulmonary hypertension the white whale or red herring in neonatal septic shock? (3) Is sepsis more like dominoes or like 52 pick-up? and (4) Is disruption of QO2/VO2 coupling a legitimate clinical concern or a laboratory anomaly? Shock, 1995 Jun, 3(6), 403 - 10 Mechanisms regulating skeletal muscle glucose metabolism in sepsis; Vary TC et al.; Carbohydrate dyshomeostasis is a characteristic feature of sepsis . Sepsis elevates glucose uptake and cellular lactate levels in muscle . The mechanisms responsible for these alterations are unknown . We examined the effects of a chronic, intra-abdominal septic abscess upon glucose uptake, the expression of the insulin receptor, glucose transporter proteins (Glut-1 and Glut-4) and mRNA, and the content of glycolytic intermediates in muscle from the hindlimb . Sepsis caused a 67% increase in glucose uptake compared with control . A differential expression of the Glut-1 and Glut-4 transporter proteins in skeletal muscle of septic rats was observed . Sepsis increased the expression of Glut-1 protein 1.7-fold . The increased Glut-1 protein correlated with a similar increase in the relative abundance of Glut-1 mRNA . In contrast, sepsis did not alter the amount of Glut-4 protein and mRNA or insulin receptor protein . The tissue content of glucose-6-phosphate was increased approximately twofold compared with control . The increase in the glucose-6-phosphate content was not associated with increased glycogen deposition in skeletal muscle of septic animals . Analysis of the glycolytic intermediates showed that only the lactate content of muscles from septic rats was significantly elevated in sepsis . The results are consistent with the hypothesis that sepsis enhances glucose uptake secondary to increased Glut-1 expression . Furthermore, once transported, glucose may be preferentially metabolized to lactate. J Crit Care, 1995 Jun, 10(2), 82 - 95 Molecular mechanisms of sepsis: molecular biology of the cell; Hayashi S et al.; Complex and interrelated biological processes are at work in the expression of the host response to sepsis . To a large degree, these processes reflect drastic changes in the molecular workings of cells of the body . The protean nature of sepsis reflects this molecular adaptation . Studies are continuing to accrue that describe aspects of this process in tissue culture, animal models, and man . However, without an understanding of the basic mechanisms of molecular biology, the understanding of this important and expanding literature is limited . This review describes the basic molecular processes involved in replication of deoxyribonucleic acid (DNA) and transcription of DNA to ribonucleic acid (RNA) in the nucleus, translation of messenger RNA into proteins and the posttranslational modifications of these proteins in the cytoplasm . It uses the process of endotoxin-induced cellular activation as its model and highlights important aspects of DNA promoter and enhancer processes in this activation . Specific examples of known promoter genes and genomic translation are described . This review serves as a "primer" for the subsequent three review articles in this series that will follow it in preceding issues. J Laryngol Otol, 1995 Jun, 109(6), 531 - 3 Audit of the treatment of tonsillar and peritonsillar sepsis in an ear, nose and throat unit; MacDougall G et al.; We became aware that a range of antibiotics were being used in our unit to treat patients suffering from tonsillitis or peritonsillar abscess (quinsy) . There appeared to be no rationale to determine which antibiotics were used, and we felt that we were possibly using expensive antibiotics when cheaper equally effective ones were available . An audit project was therefore devised to establish the current practice in the ENT Unit at the City Hospital at Edinburgh . Following a six-month prospective pilot study, a protocol for the treatment of tonsillar and peritonsillar sepsis was drawn up and subsequent practice and outcome was then audited, thus completing the audit cycle . As a result substantial savings in the cost of prescribed antibiotics have been made without compromising patient care. Intensive Care Med, 1995 Jun, 21(6), 500 - 4 Blood filtration in children with severe sepsis: safe adjunctive therapy; Reeves JH et al.; OBJECTIVE: To review the safety and efficacy of haemofiltration and plasmafiltration in children with severe sepsis . DESIGN: Retrospective case notes analysis . SETTING: University Paediatric Intensive Care Unit . PATIENTS: All children admitted to the intensive care unit between November 1985 and May 1992 with a primary diagnosis of severe sepsis who also received blood filtration therapy . INTERVENTIONS: Continuous haemofiltration (HF) 18 patients; continuous haemofiltration and plasmafiltration (PF) 9 patients . MEASUREMENTS AND RESULTS: 27 children with sepsis-induced MOSF, median age 26.6 months (range 0.33-185), median weight 12 kg (range 2.5-58), mean PRISM score 19.4 (SD 8.6), mean number of organs failing 2.78 (SD 0.9) received filtration for a median duration of 36 hours (range 2-145) . Eight (30%) survived (HF 5/18, PF 3/9) . There was no significant difference in the demographic features between the HF group and the PF group and no difference in mortality . The two groups were pooled to assess the effect of commencement of filtration on clinical wellbeing . Arterial blood gases, electrolytes, full blood examination, ventilator settings and doses of inotropes were recorded immediately prior to commencement of filtration and 18 h after commencement . Serum anion gap and osmolality were calculated using conventional formulae . There were no significant changes in the level of cardiorespiratory support, or biochemical markers of severity following commencement of filtration . Platelet count fell 32% (p = 0.029) but no bleeding was encountered . No severe complications were observed during 1222 h of filtration . No bleeding or infection was observed at the site of cannulation . One child developed haemodynamic instability following commencement of plasmafiltration necessitating abandonment of the procedure . CONCLUSION: Haemofiltration or plasmafiltration can be performed safely in children with severe sepsis but their effect on outcome remains unknown. JPEN J Parenter Enteral Nutr, 1995 May-Jun, 19(3), 234 - 8 Nitric oxide, sepsis, and arginine metabolism; Kelly E et al.; Nitric oxide is one of the most versatile molecules produced by mammalian cells . Its role in sepsis and inflammation has been the subject of intense investigation since its discovery as a cell product in 1987 . The role of arginine in sepsis and trauma has also received considerable attention, but most of the earlier studies on arginine preceded the studies on nitric oxide and the discovery that arginine serves as the nitrogen donor for nitric oxide synthesis . This review will explore the role that nitric oxide plays in sepsis and the effects of arginine metabolism on nitric oxide synthesis. Surgery, 1995 May, 117(5), 520 - 30 Hepatic metabolic response to injury and sepsis; Dahn MS et al.; BACKGROUND . Experimental reports have indicated that hepatic oxidative and synthetic metabolism may become depressed in sepsis . Because the mechanism of infection-related liver dysfunction has not been established, further study of these functional alterations could contribute to the therapeutic management of septic organ failure syndromes . However, recently controversy has arisen over the existence of these derangements that must be reconciled before further progress in this field can be made . METHODS . Splanchnic balance studies for the measurement of glucose output and oxygen consumption were used to assess hepatic function in fasted normal volunteers (n = 18), injured patients (n = 10), and patients with sepsis (n = 18) . The liver's contribution to splanchnic metabolism was estimated from a comparison of splanchnic oxygen utilization in response to increases in the liver-specific process of glucogenesis . In addition, in vivo liver albumin production was determined by using the {14C} carbonate technique . RESULTS . Glucose output after injury and sepsis was increased by 12.8% and 76.6%, respectively, compared with controls . On the basis of substrate balance studies, gluconeogenesis was estimated to account for 46%, 87%, and 93%, respectively, of splanchnic glucose output in each of the three groups . In patients with sepsis glucose output was also noted to be linearly related to regional oxygen consumption, indicating that these processes were coupled and increases in the respiratory activity of the splanchnic cellular mass could be accounted for by increases in new glucose output and gluconeogenic substrate clearance . The mean albumin synthetic rate increased during injury and sepsis by 22% and 29%, respectively, compared with normal volunteers . CONCLUSIONS . These studies cast doubt on the commonly held notion that tissue respiratory dysfunction may occur during sepsis . On the contrary, hepatic function is accelerated during hyperdynamic sepsis, and evidence indicating oxidative or synthetic functional depression is lacking. Crit Care Med, 1995 May, 23(5), 955 - 63 Strategies for blocking the systemic effects of cytokines in the sepsis syndrome; Christman JW et al.; OBJECTIVES: To review and evaluate animal and human data regarding strategies to intervene in the pathogenesis of the sepsis syndrome by specifically blocking the action of single cytokines . DATA SOURCES: The English language medical literature was reviewed, including reports of human clinical trials, animal experiments, and in vitro studies elucidating cellular and molecular interactions . STUDY SELECTION: Emphasis was placed on controlled experimental studies that elucidated the effectiveness of antibodies, soluble receptors, and receptor antagonists in intervening in the pathogenesis of the sepsis reaction . DATA EXTRACTION: This review focuses on data that directly involve the induction and regulation of protein mediators of sepsis, especially tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-8 . DATA SYNTHESIS: Information concerning the potential of cytokine blockers in modulating the sepsis reaction is presented in a logical, clinically oriented fashion . The purpose is to emphasize the potential role of these agents by focusing on the actual existing data . CONCLUSIONS: The pathophysiology of the sepsis reaction appears to involve the sequential release of cytokines . Interventions designed to specifically block the biological effects of single cytokines appear to have a role in the management of sepsis syndrome, but well-designed, prospective, randomized, placebo-controlled clinical trials in well-defined clinical populations are necessary to define this role . These trials require the cooperation of clinical and basic scientists. Crit Care Med, 1995 May, 23(5), 835 - 42 Increased serum nitrite and nitrate concentrations in children with the sepsis syndrome; Wong HR et al.; OBJECTIVES: To measure total serum nitrite and nitrate concentrations in children with the sepsis syndrome as an indicator of endogenous nitric oxide production . To determine if there is an association between total serum nitrite and nitrate concentrations and vascular responsiveness to norepinephrine . DESIGN: A prospective, clinical study . SETTING: Tertiary, multidisciplinary, pediatric intensive care unit . PATIENTS: Thirty-one children with the sepsis syndrome, 18 of whom were also hypotensive . Sixteen critically ill children without signs of the sepsis syndrome served as controls . INTERVENTIONS: Blood samples were obtained from indwelling catheters . The norepinephrine dose to reach the age appropriate, 50th percentile mean arterial blood pressure was determined in patients receiving norepinephrine . MEASUREMENTS AND MAIN RESULTS: Total serum nitrite and nitrate concentrations were measured on the first three days after the recognition of the sepsis syndrome . Patients with the sepsis syndrome had increased mean total serum nitrite and nitrate concentrations (day 1, 118 +/- 93 microM; day 2, 112 +/- 94 microM; day 3, 112 +/- 93 microM) vs . controls (43 +/- 24 microM, p < .05) on all 3 days . When sepsis syndrome patients were separated into nonhypotensive and hypotensive groups, only the patients with hypotension had increased concentrations vs . controls on all three days (p < .05) . Sepsis syndrome patients with hypotension also had higher total serum nitrite and nitrate concentrations (145 +/- 97 microM) than sepsis syndrome patients without hypotension (82 +/- 76 microM, p < .05) on day 1 . In five patients receiving norepinephrine infusions, increased total serum nitrite and nitrate concentrations were associated with higher norepinephrine requirements to maintain an age-appropriate, 50th percentile mean arterial blood pressure on each of the three study days (day 1, rs = 0.821, p < .05; day 2, rs = 0.900, p < .05; day 3, rs = 0.872, p < .05) . CONCLUSIONS: Children with the sepsis syndrome, particularly those patients with hypotension, have increased total serum nitrite and nitrate concentrations that likely reflect increased endogenous production of nitric oxide . Vascular hyporesponsiveness to norepinephrine during the sepsis syndrome may be, in part, a nitric oxide-mediated process. Anesteziol Reanimatol, 1995 May-Jun, (3), 39 - 40 {Slow-flow membrane oxygenation of blood as a method of detoxication in the treatment of patients with abdominal sepsis}; Lobakov AI et al.; The criteria of efficacy of small-flow membranous oxygenation of the blood were defined and the duration of this measure optimized in the treatment of 30 patients hospitalized at the department for abdominal surgery, Moscow District Research and Clinical Institute, after operations for abdominal diseases and purulent complications thereof performed at hospitals of the Moscow district . Small-flow membranous oxygenation of the blood brought about a trend to normalization of the peripheral blood parameters which were changed as a result of inflammation; it was conducive to normalization of the blood acid-base status and oxygen extraction by tissues, and had an immunostimulating effect in general . The level of medium-weight molecular peptides may be regarded as a criterion of the efficacy of small-flow membranous oxygenation of the blood . With an initial concentration of medium-weight molecules of at least 1 arbitrary unit, the procedure may be as short as just two hours . Under such conditions, small-flow membranous oxygenation of the blood may be considered as a specific detoxifying method. Clin Rheumatol, 1995 May, 14(3), 327 - 9 Ultrasound-guided aspiration in suspected sepsis of resection arthroplasty of the hip joint; Foldes K et al.; The authors described 17 patients who had had resection arthroplasty of the hip and who were suspected of having an infection . The resection arthroplasties had been performed for previous infection . All the patients were studied by ultrasonography to detect effusion in the pseudoarticular space . Thirteen of the 17 patients were found to have an effusion by ultrasonography . Fluid was obtained in 9 of the 13 patients by ultrasonographic-guided aspiration . The mean aspirated volume was 3 ml (range 1-25 ml) . Five of the 9 aspirates proved to be septic . The echopattern in all but one of those five with sepsis was nonechofree . Of four other patients in whom it was not possible to aspirate fluid lavage of the pseudoarticular space one yielded a positive culture . The role of ultrasonography in the diagnosis and management of patients who have undergone resection arthroplasty of the hip and who are suspected of having an infected pseudoarticular space is discussed. Pediatr Infect Dis J, 1995 May, 14(5), 362 - 6 Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal sepsis: a critical review; Da Silva O et al.; To evaluate the value of C-reactive protein and leukocyte indices in the workup of patients suspected of having infection in a neonatal intensive care setting, a literature search was conducted in all languages using MEDLINE (1966 to May, 1994), EMBASE (1988 to May, 1994), bibliographic lists of primary and review articles and personal files . Citations identified as potentially relevant were reviewed by two independent investigators; only studies meeting preset criteria for population, diagnostic test and data presentation were included . Two observers independently assessed studies using explicit methodologic criteria . All data from the articles were extracted by one observer, whereas the second reviewer checked these data for accuracy . Four of the selected studies dealt with leukocyte count and ratios . The chi square test for homogeneity of proportions revealed significant heterogeneity across studies (P = 0.014 for the ratios; P < 0.001 for white blood cell count), suggesting that test properties varied widely across studies . Fifteen of the selected studies evaluated C-reactive protein; of these six were qualitative using a latex agglutination method . Among these studies the chi square test for homogeneity of proportions was highly significant (P < 0.01), reflecting the great heterogeneity across studies . Among the nine studies that evaluated five different quantitative methods heterogeneity was again present (P < 0.001) . Because of the striking heterogeneity among the studies evaluated, pooling to give a summary point estimate of the sensitivity and specificity of the various studies was not possible and the results are reported as ranges.(ABSTRACT TRUNCATED AT 250 WORDS) Cardiol Clin, 1995 May, 13(2), 249 - 56 The cardiovascular effects of sepsis; Carleton SC; Future therapies for septic shock will likely center around the antagonism of toxins released by the infecting organism and the modification of the host response to such toxins . Until such therapies become available, patient salvage will continue to depend on the maintenance of effective circulatory function until the source of infection is eliminated . With the recognition that resuscitation is best directed toward optimization of peripheral oxygen metabolism, reduction of mortality has been achieved in recent years through the early application of invasive hemodynamic monitoring and the aggressive manipulation of the determinants of peripheral oxygen delivery . Volume loading to improve myocardial performance, transfusion to increase the oxygen carrying capacity of the blood, intubation and mechanical ventilation to maximize arterial oxygen saturation, sedation to limit unnecessary peripheral oxygen use, and pharmacologic support of supranormal peripheral perfusion requirements are the essential tenets of successful management. Pediatr Res, 1995 May, 37(5), 626 - 9 Increased plasma concentrations of interleukin-1 receptor antagonist in neonatal sepsis; de Bont ES et al.; Newborns are prone to severe infections and sepsis . Cytokines such as tumor necrosis factor-alpha and IL-1 beta play a major role in the initiation of the host response to infections . IL-1 receptor antagonist (IL-1ra) is a naturally occurring antagonist of IL-1 beta . We hypothesized that low IL-1ra plasma concentrations might contribute to the high morbidity and mortality of neonatal sepsis . We studied IL-1ra plasma concentrations during neonatal sepsis . Eleven newborns with severe infection or sepsis, 28 newborns suspected as having sepsis, and eight healthy newborns were enrolled in the study . IL-1ra plasma concentrations proved to be increased in the newborns with severe infections or sepsis (5635 +/- 411 ng/L) versus the concentrations in the suspected group (2597 +/- 433 ng/L) and the control group (273 +/- 88 ng/L) (p < 0.001) . After the start of antibiotic therapy, the IL-1ra plasma concentrations remained high during the first 16 h . The IL-1 beta plasma concentrations were increased in the group with a proven infection (78 +/- 27 ng/L) versus the suspected group (37 +/- 7 ng/L) (p < 0.05) . Interestingly, the mean Il-1RA plasma concentration is a factor 50-100 higher than the IL-1 beta plasma concentrations . We conclude that IL-1ra in newborns is produced in an amount equal to that in adults . An inadequate IL-1ra response does not seem to contribute to the increased morbidity and mortality of neonatal sepsis. New Horiz, 1995 May, 3(2), 257 - 66 Sepsis and multiple organ dysfunction syndrome: a clinical-mechanistic overview; Livingston DH et al.; Multiple organ dysfunction syndrome (MODS) is the primary cause of death in patients admitted to ICUs . Despite the development of better resuscitation, more powerful antibiotics, and more sophisticated methods for organ support, our ability to rescue patients from established MODS has not improved significantly since the syndrome was first described two decades ago . Rapid advancements in molecular biology have begun to unravel some of the potential mechanisms behind the development of this syndrome, and have suggested many potential therapeutic approaches . To effectively use these new treatment options as they become available, it is necessary to have a clear understanding of how these therapies fit into the current theories on the pathophysiology of MODS . Thus, the goal of this article is to integrate what is new in our understanding of the development of MODS with current concepts regarding potential therapies of this complex and perplexing syndrome. Infection, 1995 May-Jun, 23(3), 143 - 8 Pattern of soluble TNF receptors I and II in sepsis; Schroder J et al.; The serum levels of soluble TNF receptors I (sTNFR I) and sTNFR II were measured frequently in 14 patients with sepsis to evaluate the pattern of these TNF antagonists in relation to TNF alpha, Soluble TNFR I and II could be detected in all samples with significantly higher levels (p < 0.001) compared to healthy controls . The concentration of sTNFR I as well as sTNFR II was significantly higher in nonsurvivors compared to survivors during the first 36 h of sepsis (p < 0.001) . Levels remained elevated throughout the evaluation with maximal values in patients who died . A positive correlation exists between both receptors and between soluble receptors and simultaneously obtained sepsis score (p < 0.01) while TNF immunoreactivity detected in 80% of all samples did not correlate to soluble receptor levels or sepsis score . Soluble receptors were constantly found in the circulation representing the inflammatory state throughout the evaluation even when TNF activity was undetectable. J Intensive Care Med, 1995 May-Jun, 10(3), 145 - 52 Trauma, sepsis, and disseminated intravascular coagulation; Hardaway RM; Disseminated intravascular coagulation (DIC) was first observed clinically in a case of sepsis following severe trauma . It was postulated that the observed clotting defect and bleeding were due to the using up of clotting factors in an episode of intravascular clotting . It was also postulated that the multiple organ failure observed was due to obstruction of the microcirculation of the organs by microclots . Evidence for this process was worked out in many animal studies . It was then postulated that if these microclots could be lysed before organ necrosis was produced, organ failure could be prevented . This prevention was shown to be possible in animals . It was then tried in humans using plasminogen activators, and the approach was found to be effective . Using a low dose of plasminogen activator over a 24-hour period caused no changes in the coagulation profile or bleeding. Infusionsther Transfusionsmed, 1995 Apr, 22(2), 106 - 9 Protein synthesis in specific tissues during sepsis; Planas M et al.; BACKGROUND: The hypothesis that fractional protein synthesis rates (Ks) are tissue-specific and bidirectional during sepsis was tested in an animal model . MATERIAL AND METHODS: Ks in liver, triceps muscle, and diaphragm were measured in septic (n = 27) and control rats (n = 26) . Sepsis was induced by a reproducible model established in our laboratory (intraperitoneal injection of sterile NaOH 0.75 N at 0.075 ml/100 g of body weight) . Ks were measured using the flooding-dose method in tissue obtained from the diaphragm, liver, and from the triceps muscle . RESULTS: In hepatic and diaphragmatic tissue, Ks were significantly higher in the septic animals (Ks: 112.2 +/- 8 and 5.4 +/- 1.9, respectively) than in control animals (Ks: 78.5 +/- 13 and 2.9 +/- 1.7, respectively) . In the triceps, Ks were significantly lower in septic animals (Ks: 2.9 +/- 1.4) than in control animals (Ks: 5 +/- 1.8) . CONCLUSION: The results suggest that in septic animals the rate of protein synthesis is enhanced in tissues of priority, such as the liver, and varies in response to differences in muscle activity. Ann Thorac Surg, 1995 Apr, 59(4), 975 - 80 Neonatal extracorporeal membrane oxygenation complicated by sepsis . Extracorporeal Life Support Organization; Meyer DM et al.; The onset of sepsis in neonates while on extracorporeal membrane oxygenation (ECMO) may portend adverse results . Nevertheless, ECMO has been used as a therapy in the management of septic conditions . This study assessed morbidity and mortality in neonates in whom septic complications developed while they were on ECMO . Of 5,123 neonates in the Extracorporeal Life Support Organization Registry undergoing ECMO for nonseptic indications, 217 patients had development of septic complications . A multivariate logistic regression analysis that considered 15 pre-ECMO criteria was performed to evaluate outcome . Mortality was higher in the septic group (35% versus 17%; p < 0.002) and ECMO duration averaged 85 hours longer (p < 0.001) . Septic neonates had a greater frequency of complications including seizures, gastrointestinal bleeding, renal dysfunction, and metabolic problems (all p < 0.05) . Transfusion requirements were doubled . Oxygenator thrombi and hemofilter malfunction occurred more often in septic patients (p < 0.03) . New strategies to prevent sepsis and associated thrombotic and metabolic complications may be indicated . A critical reappraisal of continued aggressive support may be warranted when septic complications develop in neonates during ECMO. Intensive Care Med, 1995 Apr, 21(4), 302 - 9 Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients; Pittet D et al.; OBJECTIVES: To determine the incidence of systemic inflammatory response syndrome (SIRS), sepsis and severe sepsis in surgical ICU patients and define patient characteristics associated with their acquisition and outcome . DESIGN: One-month prospective study of critically ill patients with a 28 day in-hospital follow up . SETTING: Surgical intensive care unit (SICU) at a tertiary care institution . METHODS: All patients (n = 170) admitted to the SICU between April 1 and April 30, 1992 were prospectively followed for 28 days . Daily surveillance was performed by two dedicated, specifically-trained research nurses . Medical and nursing chart reviews were performed, and follow up information at six and twelve months was obtained . RESULTS: The in-hospital surveillance represented 2246 patient-days, including 658 ICU patient-days . Overall, 158 patients (93%) had SIRS for an incidence of 542 episodes/1000 patients-days . The incidence of SIRS in the ICU was even higher (840 episodes/1000 patients-days) . A total of 83 patients (49%) had sepsis; among them 28 developed severe sepsis . Importantly, 13 patients had severe sepsis after discharge from the ICU . Patient groups were comparable with respect to age, sex ratio, and type of surgery performed . Apache II score on admission to the ICU and ASA score at time of surgery were significantly higher (p < 0.05) only for patients who subsequently developed severe sepsis . The crude mortality at 28 days was 8.2% (14/170); it markedly differed among patient groups: 6% for those with SIRS vs . 35% for patients with severe sepsis . Patients with sepsis and severe sepsis had a longer mean length of ICU stay (2.1 +/- 0.2 and 7.5 +/- 1.5, respectively) than those with SIRS (1.45 +/- 0.1) or control patients (1.16 +/- 0.1) . Total length of hospital stay also markedly differed among groups (35 +/- 9 (severe sepsis), 24 +/- 2 (sepsis), 11 +/- 0.8 (SIRS), and 9 +/- 0.1 (controls, respectively) . CONCLUSIONS: Almost everyone in the SICU had SIRS . Therefore, because of its poor specificity, SIRS was not helpful predicting severe sepsis and septic shock . Patients who developed sepsis or severe sepsis had higher crude mortality and length of stay than those who did not . Studies designed to identify those who develop complications of SIRS would be very useful. Br J Surg, 1995 Apr, 82(4), 524 - 9 Outcome of patients with abdominal sepsis treated in an intensive care unit; McLauchlan GJ et al.; A group of 125 patients with abdominal sepsis admitted to the intensive therapy unit between January 1990 and June 1993 were reviewed to determine outcome . Mean(s.d.) age was 66(12) years and admission Acute Physiology And Chronic Health Evaluation (APACHE) II score 23(9) . The hospital mortality rate was 63 per cent . Factors associated with mortality included age, APACHE II score, occurrence of septic shock, chronic ill health, female sex, sepsis of upper gastrointestinal origin and failure to clear the source of sepsis (all P < 0.05) . Delay to surgery, anastomotic leakage and presence of malignancy did not influence survival significantly . Quality of life (measured by the World Health Organization performance score) at 15 months after discharge showed 24 of 32 survivors to be independent, ambulatory and capable of self care . No patient survived to become completely disabled . The factors associated with survival did not predict subsequent quality of life . Accurately defining the characteristics of this heterogeneous group of patients is a prerequisite for improved treatment, patient selection and research. Shock, 1995 Apr, 3(4), 259 - 67 The induction of accelerated thymic programmed cell death during polymicrobial sepsis: control by corticosteroids but not tumor necrosis factor; Ayala A et al.; Thymic programmed cell death (PCD) or apoptosis (Ao) is elevated during inflammation by a variety of stressors in vitro (i.e., glucocorticoids, tumor necrosis factor (TNF), prostanoids, etc.), however, little or no information is available concerning its presence in polymicrobial sepsis . To establish whether or not PCD is accelerated in the thymus following the onset of sepsis, thymocytes were harvested from C3H/HeN mice at 1, 2, 12, and 24 h following cecal ligation and puncture (CLP; to induce sepsis) or Sham-CLP (Sham), and assessed for changes in thymocyte viable cell yield, increased Ao + cells based on FACS analysis (propidium iodide staining) or by evidence of fragmentation of the genomic DNA . The results indicate that at 1 h post-CLP there were no marked changes in any of these parameters . However, by 4 h post-CLP the percentage of Ao + thymocytes increased and the septic mouse genomic DNA exhibited trace amounts of fragmentation . These changes increased in the septic animals cells through both 12 and 24 h . Alternatively, thymic viable cell yield did not significantly decrease until 12 h . Marked changes in systemic mediators, corticosterone and TNF, were also detected in septic mouse blood at all time points . In an effort to determine the contribution of these two agents to the induction of the accelerated PCD seen here, mice were randomized to receive either RU-38486 (11 beta-{p-(dimethylamino)phenyl}-17 beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one (Mifepristone); a steroid receptor blocker), polyethylene glycol (PEG)-(rsTNF-R1)2 (a TNF inhibitor) immediately following CLP.(ABSTRACT TRUNCATED AT 250 WORDS) Shock, 1995 Apr, 3(4), 235 - 51 Interleukin-1 and interleukin-1 antagonism in sepsis, systemic inflammatory response syndrome, and septic shock; Pruitt JH et al.; Interleukin-1 (IL-1) is one of several proinflammatory cytokines produced during infection, sepsis, and the systemic inflammatory response syndrome (SIRS) that serves to initiate the host inflammatory response and to integrate nonspecific immunity . Many of IL-1's biologic effects are beneficial to the host in times of stress, but when produced for extended periods of time or in excessive quantities, IL-1 contributes to morbidity and mortality . In fact, excessive IL-1 production has been directly linked to the development of hypotension, shock, multi-organ system failure, hematologic dyscrasia, and death in patients and animals with sepsis, SIRS, and septic shock . Recent research interest has focused on IL-1 inhibition to improve outcome in sepsis and septic shock . This article will review the role for IL-1 in sepsis and septic shock, and the function and status of the IL-1 receptors and IL-1 receptor antagonist in modulating IL-1 actions . The results of investigations of IL-1 inhibition in animal models and in human subjects with sepsis and septic shock will also be reviewed. Eur J Pharmacol, 1995 Mar 16, 292(3-4), 341 - 4 Effect of N-acetyl-L-cysteine on sepsis in mice; Villa P et al.; The effect of the antioxidant N-acetyl-L-cysteine was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture . N-Acetyl-L-cysteine significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity . This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture . A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate . The effect of N-acetyl-L-cysteine was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content . These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that N-acetyl-L-cysteine works as a direct antioxidant and scavenger of free radicals generated from other sources. Clin Chem, 1995 Mar, 41(3), 462 - 4 Decreased amino acid uptake by erythrocytes during postoperative sepsis; Roberts NB et al.; We describe a patient with postoperative sepsis associated with reduced ability to transport amino acids into erythrocytes . Administration of amino acid infusion showed no effect on plasma or red blood cell concentrations of the amino acids during the sepsis period . However, when the site of sepsis was removed, patient recovery was associated with marked increases of all amino acids, particularly in the red blood cells . The case illustrates the potential of red blood cells as a marker of amino acid utilization and demonstrates the association of sepsis with effects on cellular uptake. Am J Respir Crit Care Med, 1995 Mar, 151(3 Pt 1), 758 - 67 Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis; Sabharwal AK et al.; Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein primarily synthesized by the endothelium . A major fraction (approximately 85%) of TFPI remains associated with the endothelium, whereas a small fraction (approximately 15%) is secreted into the blood . In our attempts to search for a marker(s) of endothelial injury in the setting of adult respiratory distress syndrome (ARDS), we retrospectively measured plasma TFPI levels in patients at risk for and with ARDS caused by several etiologic factors . Plasma von Willebrand factor antigen (vWF-Ag), another endothelial-specific protein, was also measured in these patients . The mean plasma TFPI levels were slightly elevated (approximately 1.3-fold), whereas vWF-Ag levels were significantly elevated (approximately 3-fold) in the at-risk group as compared with those in the normal subjects . Both the TFPI (approximately 1.8-fold) and the vWF-Ag (approximately 4-fold) levels were further elevated in the ARDS group . Moreover, the sequential plasma samples from patients with ARDS had progressively increased levels of vWF-Ag and TFPI up to Days 4 and 8, respectively . Neither plasma vWF-Ag nor TFPI levels correlated with mortality in the at-risk group or the ARDS group . TFPI levels were also measured in bronchoalveolar lavage fluids (BALF) . The levels (ng/ml) were: normal subjects, 0.05 +/- 0.02 SE; at-risk group, 0.35 +/- 0.16 SE; ARDS group, 0.99 +/- 0.28 SE . Thus, the BALF TFPI levels were increased approximately 7-fold in the at-risk group and approximately 20-fold in the ARDS group relative to the value in the normal subjects . These findings indicate increased local synthesis of TFPI in the alveolar space both in the at-risk patients and in those with ARDS . In additional studies in a primate model of sepsis, lethal doses (LD100) of E . coli administered to baboons resulted in a progressive increase in TFPI levels (approximately 2-fold at 6 h), whereas sublethal doses caused only minimal increase (approximately 1.2-fold) . The vWF-Ag levels were elevated approximately 5-fold after infusion of LD100 concentrations of E . coli at 6 h and 4-fold after infusion of sublethal concentrations of E . coli at 24 h . Autopsies on animals in the LD100 group revealed pulmonary congestion, leukocyte infiltration, edema, and hemorrhage, all suggestive of acute lung injury . Thus, in the setting of acute lung injury plasma vWF-Ag appears to be considerably increased prior to significant damage to the endothelium, whereas increased plasma TFPI occurs only after severe injury.(ABSTRACT TRUNCATED AT 400 WORDS) Am J Respir Crit Care Med, 1995 Mar, 151(3 Pt 1), 706 - 12 Vascular reactivity in sepsis: importance of controls and role of nitric oxide; Yaghi A et al.; We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis . The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) in this altered vascular contractility . Rats were randomized to sepsis induced by cecal ligation and perforation (CLP) or to one of two control procedures . The Sepsis group had a jugular venous line for fluid administration, laparotomy, and CLP . Control group 1 (Control) had only a jugular venous line inserted, while group 2 (Sham) had a jugular venous line inserted and an abdominal incision . All rats were killed 24 h after surgery . Vascular contractility of small pulmonary arterial and thoracic aortic rings was assessed in vitro by obtaining cumulative dose-response curves to the contractile agonists potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2 alpha (PGF2 alpha) . Pulmonary vessels from animals in the Sepsis and Sham groups exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2 alpha compared with the Control group . In contrast, contractility of the aortic rings to KCl, PE, and PGF2 alpha was not significantly different in the three groups studied . Incubation of pulmonary and aortic vessels with NG-nitro-L-argine methyl ester (L-NAME, 10 microM) caused an increase in the response to KCl, PE, and PGF2 alpha in pulmonary vessels in Sepsis and Sham rats but not in Control rats.(ABSTRACT TRUNCATED AT 250 WORDS) J Thorac Cardiovasc Surg, 1995 Mar, 109(3), 419 - 425; discussion 425-7 Results of extracorporeal membrane oxygenation in neonates with sepsis . The Extracorporeal Life Support Organization experience; Meyer DM et al.; Use of extracorporeal membrane oxygenation for treatment of respiratory failure caused by sepsis is controversial because of concerns over survival benefit and hemorrhage-related complications . To evaluate the impact of the primary diagnosis of sepsis on outcome, we reviewed data from 6853 neonates in the Extracorporeal Life Support Organization Registry and defined two groups: group 1 (n = 1060), all patients undergoing extracorporeal membrane oxygenation with a primary diagnosis of sepsis; group 2 (n = 5793), those with any other primary diagnosis . A multivariate logistic regression analysis that considered 15 variables present before extracorporeal membrane oxygenation (including age, sex, birth weight, prior cardiopulmonary arrest, arterial blood gas results, and ventilator settings) was used to compare outcomes between groups . Survival was not different between the two groups (77%, group 1; 82%, group 2; p = 0.2480), although lung recovery was less frequent in the patients with sepsis (p = 0.0185) . Group 1 had a higher incidence of complications including seizures (odds ratio 1.446, p = 0.0346), cerebral infarct or hemorrhage (2.310, p = 0.0001), need for dialysis (1.478, p = 0.0131), hypernatremia (2.089, p = 0.0019), hyperbilirubinemia (2.423, p = 0.0001), and dobutamine use (1.918, p = 0.0001) . Neonates with sepsis are more likely to have neurologic, renal, and metabolic complications from extracorporeal membrane oxygenation but may still achieve a survival benefit equivalent to those without sepsis . From these data, extracorporeal membrane oxygenation should not be withheld from neonates solely on the basis of sepsis . Rather, management strategies should focus on limiting the incidence or severity of the common complications. Crit Care Med, 1995 Mar, 23(3), 459 - 65 Effect of sepsis on erythrocyte intracellular calcium homeostasis; Todd JC 3rd et al.; OBJECTIVES: To examine erythrocyte intracellular calcium dynamics in clinical sepsis and experimental endotoxemia . DESIGN: Prospective, multiexperimental study utilizing in vitro manipulation and evaluation of human erythrocytes . SETTING: University research laboratory . PATIENTS: Healthy, elective surgical patients, "septic" surgical patients, and normal volunteers . INTERVENTIONS: For all experimental studies, whole blood specimens were incubated with 2 micrograms/mL of Escherichia coli endotoxin (experimental) or an equivalent volume of phosphate buffered saline (control) . Incubations were performed in specimens pretreated with 0.4 mM of verapamil and/or 50 mM of dantrolene . Incubations were performed in the presence and absence of extracellular calcium . Incubations were also performed utilizing pre- and posttreatment with 1 mM of adenosine 5'-triphosphate (ATP) and/or 30 mM of adenosine . MEASUREMENTS AND MAIN RESULTS: Free cytosolic calcium concentration was determined by fluorescent spectroscopy, utilizing the calcium chelator, FURA-2AM . Sepsis was associated with a significant increase in erythrocyte intracellular calcium concentration as compared with nonseptic controls (96.26 vs . 45.38 nM; p < .001) . Similar changes could be induced by endotoxin incubation of whole blood (84.52 vs . 40.45 nM; p < .001) . This endotoxin-induced increase was independent of extracellular calcium concentration and was only partially ameliorated by calcium-channel blockade . Inhibition of intracellular calcium release was ineffective in altering the endotoxin-induced increase in the erythrocyte intracellular calcium value . In contrast, pretreatment with either adenosine or ATP minimized these increases . Posttreatment with ATP, but not adenosine, allowed partial reversal of this endotoxin-induced increase in intracellular calcium . CONCLUSIONS: Sepsis induces alterations of erythrocyte intracellular calcium homeostasis . A significant increase in free cytosolic concentrations of intracellular calcium is characteristic of this altered homeostasis . These changes are reproducible by the incubation of whole blood with endotoxin . This increase in cytosolic calcium concentration appears to be independent of extracellular calcium concentration, transmembrane calcium channels, and/or intracellular calcium stores . It can, however, be modulated through provision of high-energy phosphates and/or their precursors to the cell itself. Allergy Proc, 1995 Mar-Apr, 16(2), 85 - 7 Stevens-Johnson syndrome presenting as intravenous line sepsis; Cheriyan S et al.; A 25-year-old Hispanic female with insulin dependent diabetes mellitus (IDDM) and endstage renal disease on chronic hemodialysis was hospitalized with paroxysms of fever and chills for a day . A day after starting piperacillin for presumed intravascular line infection, she developed a maculopapular dermatitis and abnormal liver function tests, at which point the drug was discontinued . However, the rash persisted for 10 days, after which it progressively worsened . She continued to have high fevers, abnormal liver function tests, and marked leukocytosis, despite multiple negative cultures and other nondiagnostic examinations . She was treated as a patient with sepsis of unknown etiology and received multiple antibiotics on an empiric basis without response . A diagnosis of Stevens-Johnson syndrome was then made based on the triad of cutaneous dermatitis, mucosal, and hepatic involvement . She received high dose corticosteroids and her fever, dermatitis, mucosal lesions, leukocytosis, and abnormal liver function tests improved dramatically. Shock, 1995 Mar, 3(3), 210 - 5 Pentoxifylline improves survival and reduces tumor necrosis factor, interleukin-6, and endothelin-1 in fulminant intra-abdominal sepsis in rats; Lundblad R et al.; The influence of pentoxifylline (PTX) on mortality and some important mediators was studied in a model of cecal perforation with fulminant intra-abdominal sepsis in rats . Cumulative mortality was registered in three groups of animals: untreated sepsis (n = 36), sepsis + PTX 20 mg/kg/24 h (n = 24), and sepsis + PTX 80 mg/kg/24 h (n = 24) . PTX therapy was started at sepsis induction or after 4 h, and mortality was reduced from 89% in untreated sepsis to 60-66% in the PTX groups . Levels of sepsis mediators were studied in two groups: untreated sepsis and sepsis + PTX 40 mg/kg started 1 h after sepsis induction . In both groups 6-10 animals were sacrificed at 4 and 8 h to measure blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), interleukin-6 (IL-6), endothelin-1, lactate, neutrophils, and packed cell volume . Cecal perforation gave high levels of bacteria, endotoxin, TNF, IL-6, and endothelin-1, leading to dehydration, lactacidosis, neutropenia, and death . Treatment with PTX did not modify dehydration, neutropenia, or concentrations of bacteria and endotoxin . Release of endothelin-1 was delayed, TNF burst was nearly abolished, and levels of IL-6 and lactate were substantially suppressed . In summary, PTX improves survival and reduces blood concentrations of TNF, IL-6, lactate, and endothelin-1 in fulminant intra-abdominal sepsis in rats . The primary effect of PTX in this sequence is probably reduction of TNF. Support Care Cancer, 1995 Mar, 3(2), 111 - 9 Sepsis and septic shock . II . Treatment; Mayer J et al.; Mortality from septic shock is considerable despite the advantages of cardiovascular support and antibiotic therapy . This article reviews current therapy of septic shock including immunotherapy and further possibilities of septic shock treatment . The role of cytokines, their inhibitors and antibodies to endotoxin is mentioned . Although these treatments hold much promise for the future, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended. Support Care Cancer, 1995 Mar, 3(2), 106 - 10 Sepsis and septic shock . I . Definitions and pathophysiology; Mayer J et al.; Mortality from septic shock is considerable despite the advantages of cardiovascular support and antibiotic therapy . Understanding the pathophysiology of sepsis enables clinicians to institute rational intervention directed towards the pathophysiological mechanisms . This article reviews definitions of sepsis and offers a brief overview of ist pathophysiology . Current knowledge on the pathophysiological mechanism of cytokines and modulation of systemic cytokine levels during sepsis and septic shock is discussed . The important role of cytokines in sepsis and septic shock may require more detailed investigations of the cytokine pathophysiological network. Burns, 1995 Mar, 21(2), 127 - 9 Central venous catheter sepsis with weekly catheter change in paediatric burn patients: an analysis of 221 catheters; Sheridan RL et al.; To document the risk of catheter sepsis associated with central venous catheter changes every 7 days in paediatric burn patients, and analysis of data collected prospectively on 234 such catheters was performed . During an 18-month period there were 301 acutely burned children admitted to a regional paediatric burn facility of whom 53, with an average burn size of 42 per cent TBSA, required 234 central venous catheters . A central venous catheter management protocol was followed which included catheter changes every 7 days . If insertion sites were clean and uninflamed, catheters were replaced by guidewire and the original catheter tip was semiquantitatively cultured . Catheters were replaced to a new site if insertion sites appeared inflamed or catheter tips grew 15 or more colony forming units . Overall, 3.2 per cent (10.9 per cent by Centers for Disease Control definition) of central venous catheters were associated with sepsis . When catheters were replaced by guidewire from one to three times, catheter sites were used for a mean of 15.6 days without an increased rate of line sepsis . There was no difference in sepsis rates between catheters placed at a new site or replaced by guidewire . There were no deaths attributed to catheter-related sepsis . We conclude that a protocol allowing for catheter change to a new site, or replacement by guidewire, every 7 days was associated with a low risk of catheter sepsis in paediatric burn patients. Bol Asoc Med P R, 1995 Mar-Apr, 87(3-4), 42 - 5 Value of performing a chest radiograph in patients with diagnosis of "clinical sepsis"; Torres J et al.; In any infant admitted with diagnosis of "clinical sepsis", a chest radiograph is commonly obtained as a routine work-up . The purpose of this study was to establish the relationship between an abnormal chest radiograph and "clinical sepsis" in a population of infants . The clinical records and chest radiographs of 81 infants, (less than 3 month old) were reviewed . The temperature, white blood cell count, respiratory signs, symptoms, and chief complaints were recorded and compared with positive or negative chest radiographs . A statistically significant correlation with abnormality in the chest radiograph was not established . Four patients, (31%), with any respiratory signs had abnormal chest radiographs, whereas only 13, (19%) asymptomatic patients did . It was concluded that chest radiographs do not add useful information to the evaluation of a febrile infant who does not have clinical findings of pulmonary diseases . However, due to the limited population studied, it seems appropriate to continue the current recommended practice of ordering chest radiographs in febrile infants 3 months old or less. J Crit Care, 1995 Mar, 10(1), 21 - 6 Enhancement of neutrophil function by in vivo filgrastim treatment for prophylaxis of sepsis in surgical intensive care patients; Weiss M et al.; PURPOSE: To determine the kinetics of leukocyte counts and of oxygen radical production of neutrophils from postoperative/posttraumatic patients with or without infusion of filgrastim (recombinant human granulocyte colony-stimulating factor, rhG-CSF) as prophylaxis against sepsis . METHODS: Twenty postoperative/posttraumatic patients with a Therapeutic Intervention Scoring System (TISS) score greater than 30 were included in this study . In the 10 patients of the study group, filgrastim (1 microgram/kg/d) was infused continuously within the first 3 days and tapered to 0.5 microgram/kg/d on the following 4 days or until discharge from the surgical intensive care unit . Ten patients without administration of filgrastim served as controls . Oxygen radical production of isolated neutrophils of these patients was tested by N-formyl-methionyl-leucyl-phenylalanine (FMLP)- and zymosan-induced chemiluminescence from serial blood samples, taken until the 16th postoperative day . RESULTS: Compared with the first postoperative day, in vitro FMLP-induced neutrophil chemiluminescence was significantly increased during the following 4 postoperative days in the patients with filgrastim infusion; however, only during the first 2 postoperative days in the control group . The increase in the FMLP-induced neutrophil chemiluminescence was significantly greater (P < .05) in the study group than in the control group on the third and on the fourth postoperative day . Tapering of filgrastim by 0.5 microgram/kg/d in the study group resulted in a reduction of FMLP-induced neutrophil oxygen radical production within 48 hours . In contrast, zymosan-induced neutrophil chemiluminescence was not measurably affected in both groups . Leukocyte count of the study group significantly (P < .05) exceeded the leukocyte count of the control group from the third up to the 10th postoperative day . None of the patients treated with filgrastim developed sepsis; however, three patients within the control group did . CONCLUSIONS: Prolonged enhancement of neutrophil count and function induced by rhG-CSF may be useful in the prophylaxis of sepsis in posttraumatic/postoperative patients at high risk of sepsis. Am J Physiol, 1995 Mar, 268(3 Pt 1), E491 - 500 Amrinone prevents muscle protein wasting during chronic sepsis; Jurasinski CV et al.; The time course for the effects of sepsis on rates of protein synthesis, RNA contents, and translational efficiencies was measured in mixed muscles of rat hindlimb perfused in vitro 3, 5, and 10 days after induction of sepsis . Furthermore, the effect of daily injections of amrinone (5 mg.kg-1.day-1) on muscle protein synthesis was investigated . On day 3 of sepsis, decreased rates of protein synthesis in muscle from untreated septic animals or septic rats treated with amrinone resulted from a reduced food intake . When food intake became normalized to control after 5 days, rates of protein synthesis in untreated septic rats remained depressed . Treatment of septic animals with amrinone for 5 days prevented the sepsis-induced inhibition of protein synthesis by abolishing the inhibition of peptide-chain initiation and restoring translational efficiency to control values . In contrast, amrinone treatment of control rats for 5 days did not cause an accretion of muscle protein or augment protein synthesis . Ten days after induction of sepsis, there were no differences in rates of protein synthesis, RNA content, or translational efficiency in septic animals compared with control or amrinone-treated septic rats . Thus, amrinone prevented the sepsis-induced abnormalities in skeletal muscle protein synthesis. JAMA, 1995 Feb 22, 273(8), 644 - 50 Customized probability models for early severe sepsis in adult intensive care patients . Intensive Care Unit Scoring Group; Le Gall JR et al.; OBJECTIVE . To develop customized versions of the Simplified Acute Physiology Score II (SAPS II) and the 24-hour Mortality Probability Model II (MPM II) to estimate the probability of mortality for intensive care unit patients with early severe sepsis . DESIGN AND SETTING . Logistic regression models developed for patients with severe sepsis in a database of adult medical and surgical intensive care units in 12 countries . PATIENTS . Of 11,458 patients in the intensive care unit for at least 24 hours, 1130 had severe sepsis based on criteria of the American College of Chest Physicians and the Society of Critical Care Medicine (systemic inflammatory response syndrome in response to infection, plus hypotension, hypoperfusion, or multiple organ dysfunction) . RESULTS . In patients with severe sepsis, mortality was higher (48.0% vs 19.6% among other patients) and 28-day survival was lower . The customized SAPS II was well calibrated (P = .92 for the goodness-of-fit test) and discriminated well (area under the receiver operating characteristic {ROC} curve, 0.78) . Performance in the validation sample was equally good (P = .85 for the goodness-of-fit test; area under the ROC curve, 0.79) . The customized MPM II was well calibrated (P = .92 for the goodness-of-fit test) and discriminated well (area under the ROC curve, 0.79) . Performance in the validation sample was equally good (P = .52 for the goodness-of-fit test; area under the ROC curve, 0.75) . The models are independent of each other; either can be used alone to estimate the probability of mortality of patients with severe sepsis . CONCLUSIONS . Customization provides a simple technique to apply existing models to a subgroup of patients . Accurately assessing the probability of hospital mortality is a useful adjunct for clinical trials. Crit Care Med, 1995 Feb, 23(2), 394 - 9 Round table conference on clinical trials for the treatment of sepsis; Sibbald WJ et al.; OBJECTIVES: Using an evidence-based approach for a round table conference, to discuss sepsis according to its current epidemiology and clinical management, lessons which we feel can be learned by investigators from the design and conduct of previous clinical trials of drug therapy, and to describe the "optimum" clinical trials design for treatments of this syndrome . DATA SOURCES: Experts in the field of sepsis were selected and requested to apply an "evidence-based" approach to the published literature, from which recommendations would be synthesized and rated according to levels of evidence . These experts undertook a review of appropriate literature, primarily focusing on evidence presented by clinical trials . Applicable articles were searched for by individual experts, using a variety of on-line search strategies (i.e., MEDLINE, Current Contents; Clinical Medicine) . DATA EXTRACTION AND REVIEW: Presentation at the round table conference was followed by agreement by consensus amongst participants as to the grade of recommendation . Individual presentations and arguments for grading of levels of evidence will be published independently . Where possible, recommendations on individual topics were ranked according to the level of evidence presented . Levels I to V were used to rank randomized, controlled trials through case series, respectively . Grade A recommendation is supported by Level I evidence, Grade B recommendation is supported by Level II evidence, and Grade C recommendation is supported by Levels III, IV or V evidence . CONCLUSION: Recommendations for the design, conduct and analysis of future trials of sepsis therapies were summarized. Crit Care Med, 1995 Feb, 23(2), 376 - 93 An overview of mortality risk prediction in sepsis; Barriere SL et al.; OBJECTIVE: To review the evolution and development of mortality risk prediction methods as they have been applied to the management of septic patients . DATA SOURCES: Selected relevant articles from the pertinent literature . STUDY SELECTION: Theoretical and clinical data on the mortality risk identification, severity of illness scoring systems, and cytokine levels as they relate to mortality in patients with sepsis . DATA EXTRACTION: All concepts relating to mortality risk prediction, cytokines, severity of illness, and intensive care unit (ICU) mortality were explored and interrelated accordingly . DATA SYNTHESIS: In order to improve the precision of the evaluation of new therapies for the treatment of sepsis, to monitor their utilization and to refine their indications, it has been recommended that mortality risk stratification or severity of illness scoring systems be utilized in clinical trials and in practice . With the increasing influence of managed care on healthcare delivery, there will be an increased demand for techniques to stratify patients for cost-effective allocation of care . Severity of illness scoring systems are widely utilized for patient stratification in the management of cancer and heart disease . However, the use of such systems in patients with sepsis has been limited to application in clinical trial design for assurance of balance among treatment groups . Mortality risk prediction in sepsis has evolved from identification of risk factors, and simple counts of failing organs, to sophisticated techniques that mathematically transform a raw score, comprised of physiologic and/or clinical data, into a predicted risk of death . Most of the developed systems are based on global ICU populations rather than upon sepsis patient databases . A few, newer systems are derived from such databases . However, the overall discriminating ability of the various methods is similar . Mortality prediction has also been carried out from assessments of endotoxin or cytokine (interleukin-1, interleukin-6, tumor necrosis factor) plasma concentrations . While increased levels of these substances have been correlated with increased mortality, difficulties with bioassay and their sporadic appearance in the bloodstream prevent these measurements from being practically applied . The calibration of risk prediction methods comparing predicted with actual mortality across the breadth of risk for a population of patients is excellent, but overall accuracy in individual patient predictions is such that clinical judgment must remain a major part of decision-making . However, as databases of appropriate patient information increase in size and complexity, it may be possible in the future to devise a scoring system that can be relied on to assist in clinical decision-making . CONCLUSIONS: Severity of illness scoring systems are widely used in critically ill patients . However, their use in patients with sepsis has largely been limited to a means of stratification in clinical trials . As newer sepsis therapies become available, it may be possible to use such systems for refining their indications, and monitoring their utilization . Finally, as the databases supporting the systems increase in size and complexity, it may be possible to utilize them in clinical decision-making. Crit Care Med, 1995 Feb, 23(2), 265 - 71 Microvascular function and rheologic changes in hyperdynamic sepsis; Astiz ME et al.; OBJECTIVE: To investigate the rheologic changes and circulatory abnormalities at the microvascular level during severe sepsis . DESIGN: Prospective, controlled trial . SETTING: Medical and surgical intensive care units of a university-affiliated hospital . PATIENTS: Nine normal controls and eight adult patients with severe sepsis who met the study entrance criteria . INTERVENTIONS: Forearm blood flow was measured at rest and during reactive hyperemia by air plethysmography . Simultaneous hemodynamic measurements and blood samples for rheologic measurements were taken . MEASUREMENTS AND MAIN RESULTS: Red blood cell deformability index was determined using a simple filtration procedure . Leukocyte aggregation in whole human blood was detected by using a leukergy test . Expression of the neutrophil adhesion molecule CD11b/CD18 was measured using a monoclonal antibody and flow cytometry . All data were taken within 24 hrs of the patient meeting criteria for entrance into the study . Cardiac output, oxygen delivery, and oxygen consumption measurements were consistent with the hyperdynamic phase of severe sepsis . Forearm blood flow was significantly (p < .05) greater in septic patients (21 +/- 3 mL/min) than in controls (12 +/- 2 to 36 +/- 5 mL/min (p < .05), while in the septic patients, forearm blood flow during reactive hyperemia increased from 21 +/- 3 to 32 +/- 4 mL/min . The ratio of forearm blood flow during reactive hyperemia to forearm blood flow at rest was 3.2 +/- 0.1 in the controls and 1.6 +/- 0.1 in the septic patients (p < .01) . The red blood cell deformability index in whole blood was significantly (p < .01) decreased in the septic patients compared with the control subjects (0.41 +/- 0.07 vs . 0.98 +/- 0.08 mL/min) . This difference remained true when the hematocrit was adjusted to 45% (0.82 +/- 0.06 vs . 1.04 +/- 0.06 mL/min; p < .05) . Increased expression of the neutrophil adhesion molecule CD11b/CD18 was observed in septic patients (349 +/- 46 logarithmic fluorescence units) as compared with control subjects (233 +/- 26 logarithmic fluorescence units; p < .05) . Leukergy was also significantly (p < .05) increased in septic patients (17.7 +/- 3.8%) as compared with control subjects (8.9 +/- 1.6%) . A significant correlation was observed between leukergy and the expression of the neutrophil adhesion molecule CD11b/CD18 in controls and septic patients (r2 = .62; p < .01) . Leukergy was also inversely correlated with whole blood red blood cell deformability index (r2 = .28; p < .05) . CONCLUSIONS: Reactive hyperemia in the forearm is significantly diminished in patients with sepsis, suggesting impaired microvascular blood flow . Rheologic changes, including impaired red blood cell deformability, increased leukocyte aggregation, and endothelial adherence, may contribute to this abnormality by compromising effective capillary cross-sectional area. Am J Physiol, 1995 Feb, 268(2 Pt 2), H692 - 702 Hemodynamic effects of dopamine, norepinephrine, and fluids in a dog model of sepsis; Karzai W et al.; To study how sepsis affects hemodynamic responses to catecholamines and fluids, either Escherichia coli-infected (septic, n = 8) or sterile (controls, n = 6) fibrin clots were implanted intraperitoneally into 2-yr-old beagles . Hemodynamics were measured at each of four doses of dopamine (0, 5, 10, and 20 micrograms.kg-1.min-1) and norepinephrine (0, 10, 20, and 40 micrograms.min-1), before and after infusion of fluid (Ringer 40 ml.kg-1) . Septic animals had lower mean arterial pressure (MAP, P = 0.04), stroke volume index (SVI, P = 0.0001), and left ventricular (LV) ejection fraction (LVEF) (P = 0.0001) than controls . During this time, increasing doses of dopamine and norepinephrine produced corresponding increases (P < 0.001) in LVEF, SVI, and MAP . However, during sepsis, the ability of dopamine to increase MAP diminished, while its ability to increase LVEF and SVI was maintained . Conversely, the ability of norepinephrine to increase LVEF and SVI diminished, but its ability to increase MAP was maintained . During sepsis, fluids alone increased (P < 0.05) MAP, LVEF, SVI, and cardiac index (CI) . Fluids with catecholamines also significantly increased (P < 0.05) MAP with only minimal increases in LVEF, SVI, and CI . These data demonstrate that during sepsis without catecholamines, fluids improve cardiac performance and systemic pressures, but with catecholamines, fluids have minimal effects on cardiac performance and augment MAP . Furthermore, during sepsis dopamine is more effective than norepinephrine in increasing LV performance, but norepinephrine is more effective than dopamine in increasing systemic pressures. J Surg Res, 1995 Feb, 58(2), 131 - 6 Significance of altered fluidity of plasma membranes of the liver and kidney in rats with sepsis; Yoshida M et al.; The present study was conducted to investigate changes in plasma membrane fluidity of the liver and kidney in sepsis, which is the main cause of multiple organ failure . Male Wistar rats weighing 200-250 g were used in all experiments . Sepsis was induced by cecal ligation and puncture . As a control, a sham operation was performed . The time course of plasma membrane fluidity of the liver and the renal cortex in septicemic rats or in controls was studied . To evaluate the fluidity, fluorescence polarization was measured using 1,6-diphenyl-1,3,5-hexatriene . The fluorescence polarization values of liver plasma membranes increased after cecal ligation and puncture: 0.183 +/- 0.004 (mean +/- SEM), 0.194 +/- 0.008, 0.206 +/- 0.003, and 0.210 +/- 0.002 at 0, 24, 48, and 72 hr, respectively . Corresponding values for membranes of the renal cortex increased in a similar fashion . To determine whether factors involved in cell membrane damage exist in blood, the direct effects of lipopolysaccharide (LPS), platelet-activating factor (PAF), and serum from normal rats or from septicemic rats on membrane fluidity were studied . The fluorescence polarization of plasma membranes of the liver or renal cortex to which septicemic rat serum was added was higher than that of plasma membranes to which normal rat serum was added . The fluorescence polarization of liver plasma membranes was increased by LPS, but that of plasma membranes of the renal cortex was slightly decreased . In addition, the fluorescence polarization of liver plasma membranes was increased by PAF, but that of plasma membranes of the renal cortex was decreased.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Surg Oncol, 1995 Feb, 21(1), 85 - 6 Duodenal leiomyosarcoma as a cause of retroperitoneal sepsis; Pitcher M et al.; The case of a patient with a duodenal leiomyosarcoma presenting with sepsis is presented . The necrotic centre of the tumour communicated with the lumen of the duodenum without causing duodenal obstruction . Resection of the duodenum with tumour offers the only chance of cure. Trends Biotechnol, 1995 Feb, 13(2), 56 - 63 New strategies for combatting sepsis: the magic bullets missed the mark .. . but the search continues; Quezado ZM et al.; Despite the high expectations of scientists and industry, multiple clinical trials of anti-endotoxin- and anti-cytokine-based therapies for sepsis have failed to demonstrate benefit . Indeed, in some cases, the agents used were actually harmful to patients . In retrospect, perhaps the therapeutic premises on which these therapies were based were flawed . In the future, a better understanding of sepsis should lead to the development of accurate laboratory and clinical predictors that will identify when, and which, patients can benefit from a given therapy . Much has been learned from the efforts of industry and academia and, hopefully, the search for new therapies for this lethal syndrome will continue. J Paediatr Child Health, 1995 Feb, 31(1), 8 - 10 Role of routine lumbar puncture in neonatal sepsis; Kumar P et al.; OBJECTIVE: To evaluate the utility of lumbar puncture done routinely as part of complete workup in neonatal sepsis . METHODOLOGY: Two hundred and nine consecutive lumbar punctures performed in 169 neonates were prospectively evaluated for the diagnosis of meningitis over a 6 month period in a tertiary care referral neonatal unit . RESULTS: Among babies with 'suspected clinical sepsis', five (3.3%) were diagnosed to have meningitis . None of the clinically normal babies with high risk obstetric factors alone had meningitis . The lumbar puncture was traumatic in 22.9%, and in 26.3% the fluid obtained was inadequate for complete analysis . The results were inconclusive in 37% of the cases . CONCLUSION: Based on this study, routine lumbar puncture may not be required in clinically normal newborns with adverse obstetric factors . In babies with clinical sepsis, though the yield is not very high; there are no reliable clinical or laboratory markers to predict which babies will have meningitis and hence these babies would warrant a lumbar puncture. J Pediatr Surg, 1995 Feb, 30(2), 231 - 3; discussion 233-4 The protective role of enteral IgA supplementation in neonatal gut origin sepsis; Maxson RT et al.; Preterm infants and infants unable to breast feed are particularly susceptible to gut origin sepsis . Many studies have shown the benefits of breast milk in decreasing the incidence of bacterial infections in neonates . Little in vivo work has focused on prevention of neonatal gut origin sepsis with breast milk components . The aim of this study was to determine whether supplementation of a standard neonatal formula with exogenous, luminally administered, human secretory IgA protects against gut origin sepsis in a newborn rabbit model . Sixty New Zealand white rabbit pups were delivered by cesarean section 1 day preterm and divided into two groups--the IgA group (n = 26) and the non-IgA group (n = 34) . Animals were gavage-fed a standard artificial formula (KMR) twice daily . The IgA group was supplemented on days 3 and 4 with 6.25 mg/kg of human secretory IgA . The non-IgA group received an equal volume of saline . On the evening of day 3, the animals were orally challenged with Escherichia coli K100 . The quantity of bacteria that colonized the cecum was similar in the two groups . The quantity of bacteria that translocated to the mesenteric lymph node, liver, and spleen was significantly lower in the IgA group (P < .05) . The incidence of translocation to the organs was also significantly lower in the IgA group (P < .05) . The exogenous secretory IgA showed specificity to E coli K100 by ELISA . These data show that neonatal formula supplemented with human secretory IgA decreases the incidence and quantity of bacterial translocation of E coli K100 in a neonatal rabbit model.(ABSTRACT TRUNCATED AT 250 WORDS) J Infect Dis, 1995 Feb, 171(2), 469 - 72 Circulating interleukin-6 receptor in patients with sepsis syndrome; Frieling JT et al.; Concentrations of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), and soluble tumor necrosis factor receptor (sTNFR) p55 and p75 were measured in 25 patients with sepsis syndrome . Sequential blood samples were drawn from patients during a 7-h period . IL-6 concentrations were 34-763,000 pg/mL; they were higher in nonsurvivors than survivors, but the difference was not statistically significant . In septic patients, the median sIL-6R concentration was significantly lower than in 19 healthy volunteers (43 vs . 80 ng/mL) . sIL-6R concentrations in survivors were not significantly different than those in nonsurvivors . There was a negative correlation between IL-6 and sIL-6R in septic patients (r = -.72) . In patients with moderately impaired renal function, sIL-6R levels were not affected, but the concentrations of sTNFRs were significantly higher. Surg Endosc, 1995 Feb, 9(2), 178 - 82 Use of laparoscopy in the diagnosis and treatment of patients with surgical abdominal sepsis; Geis WP et al.; Patients often present to the surgeon with abdominal pain, tenderness, and fever . Many exhibit progressive sepsis due to abdominal pathology . Delay in diagnosis and treatment often occurs due to the use of multiple, time-consuming, expensive diagnostic studies . We delineate the use of diagnostic laparoscopy in subsets of patients in whom confusion exists as to the cause of abdominal sepsis--i.e., females in child-bearing years, elderly patients, obese patients, immunosuppressed patients, and patients with suppression of physical findings . The methodical assessment of the entire abdominal cavity is performed utilizing manipulation of the patient's position (Trendelenburg, supine, reverse Trendelenburg, left side up, right side up) and meticulous inspection of the entire small bowel . Diagnoses included acute appendicitis, gangrenous appendicitis, perforated appendicitis with peritonitis or abscess, gangrenous cholecystitis, ischemic bowel disease, perforating carcinoma of the colon, perforating diverticulitis with abscess or peritonitis, tubo-ovarian abscess, closed-loop small-bowel obstruction, megacolon, and perforation of the colon . Laparoscopic treatment of 96% of the patients was performed successfully and a laparoscopic-assisted approach was used in the remainder . There was one mortality (cardiac) and no major morbidity . The development of a Formal Diagnostic Exploratory Laparoscopic (FDEL) approach has aided in the assessment of each of the diagnoses of sepsis in the abdominal cavity . The diagnostic and therapeutic approach laparoscopically avoids extensive preoperative studies, avoids delay in operative intervention, and appears to minimize morbidity and shorten the postoperative recovery interval. Clin Sci (Lond), 1995 Feb, 88(2), 131 - 3 Nitric oxide synthase activity is increased in patients with sepsis syndrome; Goode HF et al.; 1 . We measured nitric oxide synthase activity in peripheral blood polymorphonuclear leucocytes from 10 patients with sepsis syndrome and 10 healthy subjects . 2 . Synthase activity was significantly higher in patients with sepsis than in control subjects (1202 +/- 579 compared with 595 +/- 544 pmol of nitric oxide min-1 mg-1 of cell protein, P < 0.05) . 3 . Activity was greatest in those patients with the larger number of organ failures, although this failed to reach significance (1489 +/- 560 in patients with three or more organ failures and 843 +/- 404 pmol of nitric oxide min-1 mg-1 of cell protein in those with less than three, P = 0.11) . 4 . This study provides evidence for the role of overproduction of the vasodilator nitric oxide in sepsis syndrome. New Horiz, 1995 Feb, 3(1), 65 - 72 Regulation and functions of nitric oxide in the liver in sepsis and inflammation; Pastor CM et al.; The liver plays important roles in metabolic and immune responses during sepsis . It is the major site of acute-phase protein synthesis and is responsible for the clearance of circulating pathogens . In addition to mediators such as cytokines and eicosanoids, numerous studies have emphasized the role of nitric oxide (NO.) in influencing hepatic function during sepsis . The induction and the distribution of inducible nitric oxide synthase in the liver, the regulation of the enzyme, and the functions of NO . in the liver are the subject of this review. New Horiz, 1995 Feb, 3(1), 123 - 38 Use of nitric oxide synthase inhibitors in animal models of sepsis; Booke M et al.; Sepsis, as a general inflammatory process, affects the whole organism, mainly because of the intense vasodilation and reduced perfusion pressures associated with it . The high mortality rates seen with sepsis are correlated with a reduction in mean arterial pressure . Therefore, the restoration of adequate arterial pressures is imperative . Nitric oxide (NO.) is at least partly responsible for the vasodilation . Inhibition of nitric oxide synthase (NOS) is, therefore, a logical approach for the treatment of sepsis . As with any other vasoconstrictive drug, NOS inhibitors are clinically indicated only in hyperdynamic sepsis . In animal models, their administration leads to an immediate restoration of blood pressure, accompanied by improved myocardial, pulmonary, and renal function . An increase in oxygen extraction prevents oxygen consumption from decreasing, despite a marked reduction in cardiac output to normal concentrations . In sepsis, virtually all regional blood flows are increased . In our experiments, no organ systems showed a reduction below preseptic baseline values when NOS inhibitors were administered . Furthermore, NOS inhibition did not cause an increase in lactate concentrations, indicating adequate nutritive organ blood flow . Consequently, NOS inhibitors seem to be beneficial and safe when administered under the right circumstances and in a controlled fashion. South Med J, 1995 Feb, 88(2), 220 - 1 Granulocyte colony stimulating factor in the treatment of alcohol abuse, leukopenia, and pneumococcal sepsis; Grimsley EW; A 32-year-old woman was admitted with alcoholism, leukopenia, and pneumococcal sepsis (ALPS) . Standard treatment consists of antibiotics, vitamin replacement, and intensive care unit support . Even with this treatment, the mortality rate is exceedingly high . In addition to standard therapy, this patient received subcutaneously 300 micrograms granulocyte colony stimulating factor (G-CSF) daily . Initial white blood cell count was 700 microL; by day 4 it had increased to 11,400 microL . She had a prolonged hospital course but was discharged in good condition 6 weeks after admission . G-CSF may be warranted in treating ALPS. Lancet, 1995 Jan 21, 345(8943), 158 - 60 Haemoglobin-based blood substitutes and sepsis; Griffiths E et al.; An important concern that has received little attention is the possible increased susceptibility to bacterial infections of patients infused with cell-free haemoglobin-based blood substitutes . We show that pyridoxalated polymerised human haemoglobin promotes fulminating Escherichia coli septicaemia in mice, which draws attention to the potential danger of such products in the clinic. Arch Biochem Biophys, 1995 Jan 10, 316(1), 70 - 6 Reactive oxygen species produced by liver mitochondria of rats in sepsis; Taylor DE et al.; Reactive oxygen species (ROS) can be generated in experimental shock states through several different mechanisms . We measured ROS production in metabolically active liver mitochondria from rats rendered septic by cecal ligation and puncture . By polarography, the State 4 and State 3 respiration rates of liver mitochondria isolated from septic animals were no different from control organelles . During oxidation of succinate, however, nonenzymatic hydroxylation of salicylic acid to 2,3-dihydroxybenzoic acid by mitochondria from septic rats was increased, indicating generation of hydroxyl radical (OH.) . Inhibition of electron transport at Complex I with rotenone had no effect on this pattern of OH . production, but rotenone and cyanide abolished the differences in OH . formation between control and septic liver mitochondria . Measurements of H2O2 release suggested that septic mitochondria will increase rates of H2O2 production in the presence of succinate . Additional investigations revealed no difference in the release of iron between septic and control mitochondria . When referenced to respiration rate, both OH . and H2O2 production were greater in septic liver mitochondria . The reproducible effect of sepsis on generation of reactive oxygen species by liver mitochondria utilizing FAD-linked but not NAD-linked substrates suggests that enhanced mitochondrial oxidative stress in sepsis is related to alterations in the activity of Complex II of the electron transport chain. J Inflamm, 1995-96, 46(1), 42 - 50 -308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter; Stuber F et al.; Tumor necrosis factor (TNF) is recognized as a central mediator of sepsis, septic shock, and multiple organ failure . These host reactions are associated with increased TNF levels in circulation, presumably due to increased TNF production . A previously described nucleotide variation at position -308 in the promoter region of the human TNF gene was shown to be associated with the clinical outcome of malaria . In this study we addressed the relevance of the -308 polymorphism for expression of the human TNF gene in response to bacterial endo- toxin in vivo and in vitro . First, we typed 80 patients suffering from severe sepsis and 153 healthy individuals and found no association of the -308 variation with incidence of the disease . In contrast, the NcoI marker in the closely linked lymphotoxin-alpha (LT-alpha) gene showed association with survivaL This discrepancy can be explained by the linkage of the TNFB2(NcoI) allele to the common TNF1 (-308) allele . Second, we generated reporter gene constructs with the promoter deletions and with both -308 variation in the context of the extended human TNF promoter region . Although such constructs were highly inducible by lipopolysaccharide (LPS) in transient transfections into a macrophage cell line, the -308 variation had no significant effect on transcription, consistent with the promoter deletion study . We conclude that the functional consequence of the -308 polymorphism may be unrelated to transcriptional response of the TNF gene to bacterial endotoxin. Vestn Khir Im I I Grek, 1995, 154(3), 9 - 12 {The pathogenesis of sepsis and the possibilities for its treatment using nondrug methods}; Kariakin AM et al.; The substantiation of views to the foci of the "cryptogenic" infection and its nature in sepsis is given . The state of the redox system, immunological status and functions of the liver and kidneys in patients with complicated sepsis are investigated . The data on the influence of nonmedicamental methods (hemodialysis, AUVIB, HBO, EHS) upon the parameters of the redox system, cellular and humoral immunity in acute sepsis patients are presented . A complex of nonmedicamental methods, most effective in correction of homeostasis disturbances in sepsis is suggested and tested . An analysis of efficiency of each of the nonmedicamental methods has shown that they statistically promote the decreasing of lethality indices and the duration of the hospital treatment. Akush Ginekol (Sofiia), 1995, 34(2), 29 - 33 {A comparison between 11 clinico-laboratory indices for the early diagnosis of neonatal sepsis}; Pecheva N et al.; The authors have compared 11 laboratory tests for diagnosis f neonatal sepsis: WBC cont, neutr . count, band count (> 8%), immature/mature neutrophil ratio (I:M > 0.2), throm . count, C reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, IgM, GIC, C3 fraction of the complement . We determine higher sensitivity and specificity of CRP (80.1%; 80%), C3 fraction of the complement (82.4%; 86.5%) and I:M ratio (96.9%) . We conclude that this tests are useful indicators of early diagnostic of neonatal infection. Akush Ginekol (Sofiia), 1995, 34(2), 1 - 4 {Risk factors for premature rupture of the amniotic sac and neonatal sepsis}; Tanchev S et al.; The aim of the study is to assess risk factors, who act directly or indirectly and mechanisms for PROM and neonatal sepsis . There has been examined 74 pregnant women and their newborn 38 infants was with proved neonatal sepsis . There has been established combination from factors for PROM (mechanical--88.4%, infectious--77.8%, and other factors--63.4%). Acta Anaesthesiol Scand Suppl, 1995, 107, 223 - 7 Optimal values for oxygen transport during hypothermia in sepsis and ARDS; Pernerstorfer T et al.; Mild hypothermia (33 degrees C to 35.5 degrees C) is reported to improve oxygenation and survival in patients with lung failure (1) . Although hypermetabolism may account for about 50% of the ventilatory demand in ARDS patients, the concept of reducing oxygen consumption (VO2) by lowering metabolic rate, has only recently gained attention (2) . Our study was aimed to test whether mild hypothermia established by continuous veno-venous haemofiltration (CVVHF), could optimize values for oxygen kinetics in ARDS patients . Overall, we recruited 27 patients with ARDS and sepsis . Prior initiation of CVVHF patients had to meet the following criteria: a) Murray score > 2.5, and hypoxaemia with PaO2/FIO2 < 200, b) hyperthermia of > 38 degrees C, c) cardiovascular instability requiring inotropic support . Evaluation of cardio-respiratory data was performed within four different phases (I = before, II + III during and IV = after CVVHF) every 6 hours . Core temperature as derived from the thermistor of pulmonary artery catheter was aimed to be between 35.0 degrees C and 36.5 degrees C . Optimal values for oxygen delivery (DO2) (> 550 mL/min/m2) and VO2 (> 160 mL/min/m2) were defined according to Shoemaker and achieved by fluid loading, transfusion and inotropic support (3) . Septic shock occurred in 10 of 14 nonsurvivors (nons) and 2 of 13 survivors (surv) . Mean values for DO2 and VO2 were calculated at different body temperature ranges . While at 37 degrees C DO2 was identical between surv and nons, (663 +/- 128 versus 666 +/- 127 means +/- SD) moderate hypothermia led to a small decrease of DO2 in surv and a significant decrease in nons (632 +/- 134 versus 605 +/- 128 mL/min/m2) at 35 degrees C . Concerning VO2 during hypothermia, there was a significant drop in nonsurvivors while in survivors the decrease was less pronounced . We could demonstrate a decrease in DO2 and VO2 during mild hypothermia during CVVHF . However, decreases in nonsurvivors were more pronounced than in survivors . These results suggest that the inability to achieve optimal values for DO2 and VO2 during mild hypothermia induced by CVVHF could serve as a prognostic sign for fatal outcome . Although oxygen consumption is decreased during hypothermia, hypoxaemia may result due to alterations of the oxygen transport on a cellular basis . The relationship between oxygen transport and temperature during CVVHF therefore deserves further studies. Acta Anaesthesiol Scand Suppl, 1995, 107, 219 - 22 Pentoxifylline and oxygen consumption in severe sepsis--a preliminary report; Castanon-Gonzalez JA et al.; OBJECTIVE: To demonstrate that pentoxifylline (PTX) and not placebo improves oxygen consumption (VO2) in critically ill patients with severe sepsis . SETTING: Multidisciplinary intensive care unit in a university affiliated hospital . DESIGN: A randomized, double blinded clinical trial comparing 300 mg of PTX administered in a 120 min iv infusion with an identically looking placebo . PATIENTS: 13 patients (9 men and 4 women) average age 39 (24-62) years old received PTX, and 12 patients (5 men and 7 women) average age 38 (21-83) years old received placebo . All satisfied ACCP/SCCM criteria for severe sepsis . MEASUREMENTS AND INTERVENTIONS: Patients fulfilling criteria for severe sepsis was identified on admission, cardiac output, DO2 and VO2 were measured by thermodilution and standard oximetric technics after adequate volume replacement at baseline, 60 and 120 during infusion . F-test of analysis of variance was used to test hypothesis about differences of DO2 and VO2 by group, by time and for the interaction terms, a "p" value < 0.05 was considered significant . RESULTS: Evaluation of baseline measurements of both groups revealed no significant difference in any haemodynamic function or oxygen transport variables . The average VO2 difference (0-120 min) between groups was 21 mL/min.m2 and it was higher in the experimental group, however, this difference was non significant . CONCLUSION: We think that the trend in VO2 followed by the experimental group is clinically important . If this difference is sustained we will probably be able to demonstrate our hypothesis. J Perinat Med, 1995, 23(3), 167 - 74 Concentration of purine compounds in the cerebrospinal fluid of infants suffering from sepsis, convulsions and hydrocephalus; Schmidt H et al.; Catabolites of purine