Sepsis

Chin Med J (Engl), 1992 Jan, 105(1), 34 - 8
The role of Kupffer cells in the development of hepatic dysfunction during sepsis; Meng XJ et al.; The effect of Kupffer cell blockade on hepatic function during sepsis was evaluated in this study . Methyl palmitate suspension 100 mg/100 g administered intravenously suppressed the phagocytic activity as the phagocytic index K decreased from 0.0493 +/- 0.0089 to 0.0150 +/- 0.0035 in rats . Sepsis was produced by the method of cecal ligation and needling perforation (CLP) . At the end of 15 hours after CLP the hepatic adenosine triphosphate (ATP) level and ketone body ratio decreased significantly . But in rats pretreated with methyl palmitate 24 hours prior to CLP, the ATP level returned to the normal control level (1.6906 +/- 0.06-2.2323 +/- 0.13 mumol/g) and ketone body ratio remained at significantly higher values (0.26 to 0.68) . After CLP, the liver lipoperoxide (LPO) concentration increased and glutathione (GSH) contents decreased significantly . When the septic rats were pretreated with methyl palmitate, both the LPO and GSH returned to the normal control level (62.69 +/- 1.7 to 44.62 +/- 2.12 and 159.85 +/- 9.7 to 222.27 +/- 11.34) . It is concluded that the hepatic dysfunction is modulated at least to a greater extent by many of the toxic mediators released by the activated Kupffer cells during sepsis.

J Am Board Fam Pract, 1992 Jan-Feb, 5(1), 89 - 91
Association of Escherichia coli sepsis and galactosemia in neonates; Barr PH; Galactosemia in newborns and infants is associated with the following symptoms: jaundice, hepatomegaly, failure to thrive, feeding difficulties, hypoglycemia, convulsions, lethargy, amino-aciduria, cataracts, hepatic cirrhosis, ascites, and mental retardation . If the preliminary evaluation indicates galactosemia, there is high risk for E . coli sepsis and death . Strong consideration should therefore be given for early antibiotic therapy in infants with suspected galactosemia in spite of the absence of clinical signs or symptoms of sepsis.

Nutr Hosp, 1992 Jan-Feb, 7(1), 17 - 22
{Artificial enteral nutrition in sepsis patients}; Ortiz Leyba C et al.; The importance of avoiding bacterial translocation in critical patients in order to reduce the risk of multiorganic failure has led to an insistence on maintaining the enteral nutrition method in different clinical situations . The present study examines the possible alternative of enteral nutrition using an intact protein polymer and medium chain triglyceride diet in critical patients with sepsis . For this purpose, a prospective study was conducted on 20 patients who received this diet for a period of 20 days . In 16 cases, a jejunostomy catheter was used, and in the remaining 4, a nasogastric tube . 6 of the total patients died . The results obtained show a recovery of the visceral markers (prealbumin, transferrin and retinol-binding protein) of significant statistical importance . The improvement in albumin was discarded due to simultaneous intake of seroalbumin received by the patients . The nitrogenated balance and height creatinin index improved, whereas there was no increase in hepatic enzymes . In conclusion, this enteral diet is a perfectly valid alternative to parenteral nutrition in septic patients.

J Clin Neurophysiol, 1992 Jan, 9(1), 145 - 52
The electroencephalogram in sepsis-associated encephalopathy; Young GB et al.; To define the EEG and associated clinical features of septic encephalopathy, we studied 62 patients with positive blood cultures . Patients were divided into three clinical groups: nonencephalopathic (NE), mildly encephalopathic (ME), and severely encephalopathic (SE); the latter two groups had diffuse cerebral dysfunction . EEGs were classified into five groups: normal, excessive theta, predominant delta, triphasic waves, and suppression or burst suppression, in ascending order of severity . The EEG (1) was more sensitive than our clinical criteria for encephalopathy, (2) showed features that were, when considered with clinical and laboratory characteristics, compatible with a potentially reversible encephalopathy, and (3) had well-defined categories that correlated with percent mortality, even within a single clinical group . We conclude that the EEG is a sensitive index of brain function in septic encephalopathy and that it is especially useful in the intensive care monitoring of patients with sepsis.

Am J Perinatol, 1992 Jan, 9(1), 28 - 33
Fetal monitoring in perinatal sepsis; Day D et al.; To evaluate the utility of conventional electronic fetal monitoring in detection of established perinatal sepsis, we conducted a case-controlled study of fetal monitor results in 18 patients delivering newborns with sepsis . Eleven of the 18 newborns (61%) demonstrated clinically reassuring fetal heart rate patterns, not significantly different from controls (p = 0.80) . No pattern predictive of presumed perinatal sepsis could be identified . Obstetric factors traditionally associated with increased risk of perinatal infection, such as long duration of labor, use of internal fetal monitoring, and increased number of vaginal examinations were not significantly different from controls . Preterm rupture of membranes greater than 24 hours occurred in less than 50% of the cases . Clinical diagnosis of chorioamnionitis was established in only one third of the patients who delivered newborns with sepsis . In this study, use of conventional electronic fetal monitoring did not accurately identify newborns with presumed intrauterine infection.

Arch Dis Child, 1992 Jan, 67(1 Spec No), 44 - 7
Reduced use of surface cultures for suspected neonatal sepsis and surveillance; Dobson SR et al.; Data on infection in a neonatal unit were collected prospectively for seven years . After the first four years, the number of surface cultures obtained from neonates with suspected sepsis and for surveillance was reduced . Rates of systemic infection (sepsis and meningitis) were not significantly different in the four years before and the three years after this change . Reduction in surface culture information made no observable difference to detection of colonisation in neonates with early onset sepsis (within first 48 hours of life) nor to antibiotic choice in late onset sepsis . Decisions concerning the length of antibiotic course in suspected infection were not adversely affected . Reduction in the number of surface cultures led to considerable saving of time, effort, and cost while appearing safe in terms of clinical practice and outcome.

Scand J Infect Dis, 1992, 24(3), 361 - 8
Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis; Hamilton G et al.; The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis . Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure . The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days . Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0) . These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemostasis, 1992, 22(1), 17 - 24
Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: determination of prothrombin fragment 1 + 2 and other markers; Okamoto K et al.; To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC) . In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7% . F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy . Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter . The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis . In addition, the levels of serum albumin in the two groups were similar . These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy . It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Surg Suppl, 1992, (567), 43 - 6
Teicoplanin vs cephradine and metronidazole in the prophylaxis of sepsis following vascular surgery: an interim analysis of an ongoing trial; Antrum RM et al.; This paper presents further preliminary results of a trial of the prophylaxis of sepsis in 165 patients undergoing vascular surgery . The efficacy and safety of a single dose of teicoplanin was examined and compared with three doses of cephradine plus metronidazole . No significant differences were detected in the prophylactic efficacy in either group . The first interim report indicated abnormalities in liver function, maximum at 7 days, in both groups . These findings are confirmed in this second interim report . Raised levels of GGT and alkaline phosphatase are more prominent in patients receiving teicoplanin . Liver function improved by 28 days, however, suggesting that any abnormality is transient.

Clin Immunol Immunopathol, 1992 Jan, 62(1 Pt 2), S11 - 7
The role of tumor necrosis factor in sepsis; Spooner CE et al.; There is an increasing incidence of sepsis among hospitalized patients . Also, high mortality associated with sepsis and septic shock persists despite appropriate antibiotic therapy . Recent investigations have demonstrated that bacterial antigens stimulate a cascade of cellular mediators or cytokine release . In sepsis and septic shock the response of these cytokines often exceeds natural downregulation and leads to multisystem organ failure and even death in an unacceptably high number of patients . Many investigative studies have shown that tumor necrosis factor (TNF) is the prime mediator of the inflammatory response seen in sepsis and septic shock . Sepsis management in the future will include immune modulating therapy directed against the deleterious effects of cytokines, specifically TNF . This article reviews the current problem of sepsis and the evidence to support the role of TNF in sepsis . also, recent studies employing monoclonal antibodies against TNF as well as considerations for future studies are discussed.

Eur J Cancer, 1992, 29A(1), 81 - 6
Predicting septic complications of chemotherapy: an analysis of 382 patients treated for small cell lung cancer without dose reduction after major sepsis; Radford JA et al.; The incidence and risk of septic complications in 382 patients treated for small cell lung cancer with combination chemotherapy at a single centre have been analysed . Full protocol doses were employed throughout with no dose reduction after episodes of severe or life-threatening sepsis (SLTS) . 50 (13%) patients experienced 66 episodes of SLTS associated with 1978 cycles of chemotherapy (3.2% cycles affected) . 20 (5.2%) patients died due to sepsis (SD) of whom only 4 had experienced SLTS with a previous cycle of treatment . The others died as a result of their first septic episode . A model comprising four variables, age (< or = 50 or > 50 years), Karnofsky performance status (KP < or = 50 or > 50), treatment (two- or three-drug regimen) and previous sepsis (SLTS or no SLTS with previous cycles) was found to satisfactorily describe the incidence of SLTS and SD in the study population and once validated in another patient groups this model should allow identification of high-risk individuals before treatment starts . If so, we propose that high-risk patients (age > 50 years, KP < or = 50, treatment with three-drug regimen) receive 50% of protocol doses in the first cycle of treatment with escalation to 75% and eventually 100% doses in subsequent cycles if sepsis does not supervene . Those with one or two risk factors present run a relatively low risk of SLTS or SD and we consider that full-dose chemotherapy should be used throughout in these individuals.

Acta Clin Belg, 1992, 47(1), 30 - 41
Pulmonary arterial hypertension in sepsis and the adult respiratory distress syndrome; Spapen H et al.; Pulmonary arterial hypertension, defined as a mean pulmonary artery pressure exceeding 20 mmHg has been observed both in experimental animal and human sepsis, even before development of the adult respiratory distress syndrome . In this article we review several mechanisms that have been invoked for the pulmonary arterial hypertension associated with sepsis (and the adult respiratory distress syndrome): obstruction of the pulmonary microcirculation with microthrombi composed of platelets and leukocytes, and active pulmonary vasoconstriction induced by the autonomous nervous system, hypoxia or vasoactive humoral factors ("mediators") . Some of these mediators, in particular serotonin and arachidonic acid metabolites have been the subject of substantial research and therapeutic manipulation . Since pulmonary arterial hypertension imposes an increased afterload to the right ventricle and because right ventricular dysfunction appears to be a major determinant of the outcome of sepsis, the study of the mechanisms involved in pulmonary arterial hypertension may lead to improved management of sepsis and septic shock.

Crit Care Med, 1992 Jan, 20(1), 11 - 6
Intra-abdominal sepsis alters tumor necrosis factor-alpha and interleukin-1 beta binding to human neutrophils; Simms HH et al.; OBJECTIVE: To determine the effects of intraabdominal sepsis on polymorphonuclear leukocyte tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) receptor expression . DESIGN: Prospective, randomized comparison between patients undergoing elective colon surgery vs . patients with intra-abdominal sepsis . SETTING: Tertiary-care center with all patients with intra-abdominal sepsis in a surgical ICU environment . PATIENTS: Group 1 (n = 7) represents control patients who underwent elective colon surgery without intra-abdominal sepsis . Group 2 (n = 10) represents patients with intra-abdominal sepsis . MEASUREMENTS AND MAIN RESULTS: Polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression +/- stimulation of the oxidative burst was measured using 125I TNF-alpha and 125I IL-1 beta . Superoxide anion production and candicidal activity were measured in the presence of TNF-alpha and IL-1 beta . Group 2 patients expressed fewer TNF-alpha and IL-1 beta receptors on their cell surface, and stimulation of oxidative burst reduced TNF-alpha and IL-1 beta receptor expression in group 2 more than in group 1 . Diminished TNF-alpha and IL-1 beta binding reduced superoxide anion production by group 2 polymorphonuclear leukocytes . Decreased TNF-alpha binding but not IL-1 beta, reduced polymorphonuclear leukocyte candicidal activity by group 2 polymorphonuclear leukocytes . CONCLUSIONS: a) Intra-abdominal sepsis reduces polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression . b) Expression of these surface receptors is altered by stimulation of the polymorphonuclear leukocyte oxidative burst . c) Diminished TNF-alpha and IL-1 beta receptor expression is associated with functional impairments in polymorphonuclear leukocyte activity.

Klin Wochenschr, 1991 Dec 15, 69(21-23), 969 - 74
Reactive oxygen species, antiproteases, and cytokines in sepsis; Wendel A; Although the shock syndrome is recognized as a form of "mediator poisoning", a plethora of details is hardly converging into a coherent concept of chronological and molecular order . As a model for organ failure in septic shock, three alternative experimental approaches with a common pathology are presented: When galactosamine-sensitized mice receive either lipopolysaccharide or leukotriene D4 or tumor necrosis factor alpha they develop fulminant hepatitis within few hours with a lethal outcome within one day . Detailed pharmacological intervention studies allow to conclude that endotoxin-induced leukotriene D4 release induces a transient ischemia by the known vasoconstrictive action of this eicosanoid . A following reperfusion/reoxygenation phase gives rise to superoxide formation which inactivates alpha 1 proteinase inhibitor . Thus a serine protease becomes active which is responsible for the processing of a monocytic tumor necrosis factor alpha precursor to be released into the circulation after proteolytic cleavage . By this sequence the final central mediator of shock and sepsis becomes systematically abundant . The concept arising from these studies reconciles previously known findings and provides a link between the role of reactive oxygen species in inflammation, the balance of proteases and antiproteases in the extracellular space and the release of the cytokine tumor necrosis factor in sepsis and shock.

Klin Wochenschr, 1991 Dec 15, 69(21-23), 1004 - 8
Oxygen radicals--an important mediator of sepsis and septic shock; Brigham KL; There is considerable evidence to implicate aggressive species of oxygen in the pathogenesis of organ dysfunction consequent to sepsis and septic shock . The inflammatory process appears to participate ubiquitously in this setting . A characteristic of inflammation is the involvement of activated neutrophils and their generation of aggressive oxygen species . Such species may both directly injure cells proximal to the oxidant generating cells, and may inactivate any proteolytic mechanisms normally protective against proteolytic injury caused by neutrophil elastase and other proteolytic enzymes released during inflammation . The offending agent in sepsis is most commonly envisioned as bacterial lipopolysaccharide, or endotoxin . Infusion of endotoxin into animals can reproduce much of the pathophysiology of sepsis and septic shock . In addition, administration of endotoxin to cultured cells, particularly endothelial cells, can cause responses consistent with a sequence of events that occurs in intact animals and humans . In both experimental models, it appears that aggressive oxygen species are important actors in the scenario eventuating in cell or organ injury . Of importance, the toxic consequences of these free radicals probably occurs in relatively protected spaces, including microenvironments created by close adherence between inflammatory cells and endothelial cells and the cell interior . For those reasons, the potential for antioxidants as therapy should include consideration of the volume of distribution of such substances . It is probably important that antioxidants access excluded spaces including cell interiors in order to have their maximum effect in this setting . We have studied ina preliminary way the effects of n-acetyl-cysteine, a highly permeable free radical scavenger and anti-oxidant, in patients with established ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Chest, 1991 Dec, 100(6), 1703 - 11
Effect of PGE1 on altered distribution of regional blood flows in hyperdynamic sepsis; Raper RF et al.; Since the sepsis syndrome is associated with depressed vascular reactivity, it may be incorrect to assume that pharmacologically mediated changes in cardiac output will be proportionately distributed at the regional level of the circulation . We examined the effect of hyperdynamic sepsis and the concurrent administration of the vasodilatory prostaglandin (PGE1) on the regional distribution of blood flows (Q) in unanesthetized sheep rendered septic by cecal ligation and perforation . Systemic Q progressively increased throughout a 48-h study period after cecal ligation and perforation . Simultaneously, organ Q, measured by the radioactive microsphere technique, was depressed to the pancreas, but increased to the heart, gallbladder, brain, and colon; the increased Q to both heart and gallbladder was greater than the simultaneous increase in systemic Q in this septic study . With the infusion of PGE1 (1 microgram/kg/min), mean arterial perfusing pressures fell, while the cardiac index increased further over that recorded during the 48-h septic study . Despite this depression in arterial pressures, the only significant effect of PGE1 on the interorgan distribution of Q was in the renal circulation, where it was demonstrated that kidney Q fell . We conclude that (1) hyperdynamic and normotensive sepsis exerted nonhomogeneous effects on the distribution of organ Q, and (2) an increased systemic Q during PGE1 infusion was proportionately distributed to all organs, except the kidneys, where Q paradoxically fell . The latter finding suggests that the regulation of kidney Q may be depressed across the normal range of arterial perfusing pressures in the sepsis syndrome . Further investigation is essential to understand the effect of clinical interventions on the control of tissue O2 flux at both the regional and microregional levels of the circulation.

Clin Orthop, 1991 Dec, (273), 113 - 8
Periprosthetic knee sepsis . The role of irrigation and debridement; Hartman MB et al.; Thirty-three infected total knee arthroplasties were treated by irrigation, debridement, and intravenous antibiotics . These cases were retrospectively reviewed with an average follow-up period of 4.5 years . There were 12 revisions and 21 primary arthroplasties in the series . Thirty-two knees were openly irrigated and debrided, and one was arthroscopically treated . In 20 of 33 knees, infection recurred--a reinfection rate of 61% . The authors attempted to identify factors influencing success and failure of infection eradication . There was a statistically significant improvement in the success rate of knees irrigated and debrided within four weeks of index surgery (p less than .05) . No statistically significant correlation was found between success and failure with regard to gender, age, preoperative diagnosis, previous surgery, length of intravenous antibiotics, or time from clinical symptoms to debridement . The authors believe that irrigation and debridement have a role in the immediate postoperative period . Caution should be used in periprosthetic knee infection appearing greater than four weeks from index surgery.

Surg Clin North Am, 1991 Dec, 71(6), 1175 - 85
Management of intra-abdominal sepsis; Munson JL; The management of intra-abdominal sepsis includes drainage of septic foci, debridement of devitalized tissue, and prevention of continuing peritoneal contamination . An algorithm is presented as an aid to the thought process.

Infect Dis Clin North Am, 1991 Dec, 5(4), 793 - 805
Sepsis syndrome . New insights into its pathogenesis and treatment; Bone RC; Recent insights into the pathogenesis of sepsis and its sequelae have opened up new approaches to treatment . For maximum effectiveness, however, treatment must be given as early as possible in the course of illness--but only to patients who are at high risk of developing shock . The definition of sepsis syndrome outlined in this article provides a method by which to identify such patients before the onset of shock.

Am J Physiol, 1991 Dec, 261(6 Pt 2), R1507 - 12
Increase in hepatic blood flow during early sepsis is due to increased portal blood flow; Wang P et al.; Although hepatic blood flow increases significantly during early sepsis {as produced by cecal ligation and puncture (CLP)}, it is not known whether this is due to the increase in portal or hepatic arterial blood flows . To study this, rats were subjected to CLP, after which they and sham-operated rats received either 3 or 6 ml normal saline/100 g body wt subcutaneously (i.e., all rats received crystalloid therapy) . Blood flow in various organs was determined by using a radioactive microsphere technique at 5 and 20 h after CLP or sham operation . Portal blood flow was calculated as the sum of blood flows to the spleen, pancreas, gastrointestinal tract, and mesentery . Total hepatic blood flow was the sum of portal blood flow and hepatic arterial blood flow . A significant increase in portal blood flow and in total hepatic blood flow was observed at 5 h after CLP (i.e., early sepsis), and this was not altered by doubling the volume of crystalloid resuscitation after the induction of sepsis . In contrast, hepatic arterial blood flow during early sepsis was found to be similar to control; however, it was significantly reduced in late sepsis (i.e., 20 h after CLP) . Cardiac output was significantly higher than the control in early sepsis . However, even in late sepsis, cardiac output and total hepatic blood flow were not significantly different from controls . These results indicate that the increased total hepatic blood flow during early hyperdynamic sepsis is solely due to the increased portal blood flow.

J Trauma, 1991 Dec, 31(12), 1663 - 70
Interleukin 6--a potential mediator of lethal sepsis after major thermal trauma: evidence for increased IL-6 production by peripheral blood mononuclear cells; Schluter B et al.; We studied the plasma levels of the acute phase mediator interleukin 6 (IL-6) in 21 severely burned patients (burn injuries ranging from 24% to 75% total body surface area) . The posttraumatic course of the IL-6 plasma levels was closely related to the clinical outcome . The nonseptic survivors as well as survivors with suspected sepsis (n = 14) exhibited maximal amounts of IL-6 (251 +/- 32 pg/mL) during the first 3 days post-burn, which subsequently returned to values within the normal range (days 30 to 50; 26 +/- 8 pg/mL) . In the nonsurvivors (n = 7) IL-6 concentrations permanently increased (up to 1,921 +/- 356 pg/mL) until death (days 10 to 19) resulting from sepsis with consecutive multiple organ failure . Peripheral blood mononuclear cells (PBMCs) of patients expressed IL-6-specific mRNA in vivo at high levels in contrast to the PBMCs of healthy donors . In addition, the spontaneous and PHA-induced in vitro production of IL-6 by patients' PBMCs was enhanced compared with healthy controls, whereas no significant differences were obtained with bacterial endotoxin (LPS) . The findings suggest that interleukin 6 is a potential mediator of lethal sepsis after major thermal trauma.

Kokyu To Junkan, 1991 Dec, 39(12), 1209 - 14
{Alterations in number of rabbit myocardial beta-adrenergic receptors in endotoxic shock: down regulation in hyperdynamic sepsis model and effects of cytokines administration}; Yahagi M et al.; We investigated alterations in myocardial beta- and beta 1-adrenergic receptor (BAR and B1AR) number during hyperdynamic state induced by endotoxin or cytokines . {METHODS} Twenty-nine Japanese White rabbits were divided into 2 groups . Hearts were removed 18 h after intraperitoneal administration of sterile saline (SAL) or E . coli endotoxin (LPS; 50 micrograms/kg) (Group E, n = 12), or 3 h after intravenous injection of SAL or cytokines (interleukin 1-beta; 5 micrograms/kg followed by 25 ng/kg/min for 2 h, or tumor necrosis factor; 5 micrograms/kg) (Group C, n = 17) . BAR and B1AR numbers were determined in myocardial membranes from rabbit left ventricles with techniques of radioactive ligand binding study . We used {3H} dihydroalprenolol (3H-DHA) as radioactive ligand, and specific 3H-DHA binding to BARs was defined as the difference between the presence and the absence of 10 microM propranolol . B1AR number was assessed through the specific binding of 3H-DHA in the presence of ICI 118, 551 (5 x 10(-8) M), a highly selective beta 2-adrenergic receptor antagonist . In Group E, mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) (by thermodilution) were measured under pentobarbital sodium anesthesia before excision of hearts . {RESULTS} In Group E, CO was significantly (p less than 0.05) increased in rabbits injected with LPS (E-LPS) as compared with that in rabbits injected with SAL (E-SAL) (E-LPS; 0.75 +/- 0.02 l.min-1, E-SAL; 0.61 +/- 0.05 l.min-1, mean +/- SEM) . MAP and HR were slightly decreased in E-LPS but not significantly . Maximum binding (Bmax) of 3H-DHA to BARs was significantly (p less than 0.05) decreased by 18% in myocardial membranes from E-LPS compared to E-SAL (E-LPS; 48.2 +/- 4.3 fmol/mg protein, E-SAL; 58.9 +/- 2.9 fmol/mg protein, mean +/- SEM) . Similarly, Bmax of 3H-DHA to B1ARs was decreased by 18% in E-LPS, although no statistical significance was detected . In Group C, both BAR and B1 AR number was slightly, but not significantly decreased 3 h after administration of cytokines . {CONCLUSION} These data suggest that down regulation of cardiac BARs may occur during hyperdynamic stage of endotoxic shock.

Metabolism, 1991 Nov, 40(11), 1147 - 51
Tissue metabolite levels in different types of skeletal muscle during sepsis; Angeras U et al.; The effect of sepsis on energy and metabolite levels in the white, fast-twitch extensor digitorum longus (EDL) and the red, slow-twitch soleus (SOL) muscles was studied in rats . Sepsis was induced by cecal ligation and puncture (CLP) . Control rats were sham-operated . Sixteen hours later, metabolite levels in muscle tissue were determined . Adenosine triphosphate (ATP) levels and energy charge were reduced during sepsis in SOL, but were unchanged in EDL muscles . In contrast, phosphocreatine (PCr) concentration was reduced during sepsis in EDL, but not in SOL . Tissue glycogen levels were reduced and lactate concentrations were increased in both muscles during sepsis . Results suggest that sepsis affects energy metabolism differently in different types of skeletal muscle . Tissue lactate accumulation may be consistent with muscle hypoperfusion following CLP, although other mechanisms may also be involved.

Chest, 1991 Nov, 100(5), 1397 - 403
Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome; Pacht ER et al.; The adult respiratory distress syndrome (ARDS) is a devastating clinical illness characterized by refractory hypoxemia and high-permeability pulmonary edema . Reactive oxygen species such as hydrogen peroxide and hypochlorous acid may play a key role in the pathogenesis of the acute lung injury . Glutathione (GSH) is a tripeptide that is able to react with and effectively neutralize oxidants such as hydrogen peroxide and hypochlorous acid . The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total GSH compared to normal subjects (21.7 mumols +/- 7.8 mumols vs 91.8 mumols +/- 14.5 mumols; p = 0.002) . In addition, if GSH was measured in unconcentrated bronchoalveolar lavage (BAL) fluid and indexed to total BAL protein, there was also a deficiency in patients with ARDS compared to normal subjects (0.004 +/- 0.003 nmol of GSH per microgram of total protein vs 0.026 +/- 0.005 nmol of GSH per microgram of total protein; p = 0.002) . Since patients with ARDS are subjected to an increased burden of oxidants in the alveolar fluid, principally released by recruited neutrophils, this deficiency of GSH may predispose these patients to enhanced lung cell injury.

Crit Care Med, 1991 Nov, 19(11), 1339 - 47
Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study . The Ibuprofen Study Group; Haupt MT et al.; OBJECTIVE: To evaluate the safety and physiologic actions of ibuprofen in patients with severe sepsis . DESIGN: Randomized, double-blind, placebo-controlled trial . SETTING: Three university hospital medical ICUs . PATIENTS: Twenty-nine patients with clinical evidence of sepsis and the need for hemodynamic monitoring with a pulmonary artery flotation catheter . INTERVENTIONS: Thirteen patients received placebo and 16 received ibuprofen that consisted of 600 mg (n = 11) or 800 mg (n = 5) iv over 20 mins, followed by three 800-mg doses administered as a rectal solution every 6 hrs . The initial iv dose was given within 4 hrs of the presumptive diagnosis of sepsis . MEASUREMENTS AND MAIN RESULTS: The peak circulating total ibuprofen concentration after the iv dose (49.4 +/- 4.5 micrograms/mL, mean +/- SEM) was higher than peak concentrations after the three rectal doses (17.0 +/- 2.7, 16.4 +/- 3.0, 16.0 +/- 3.1 micrograms/mL) . Both routes of ibuprofen administration were well tolerated . Frequent monitoring for gastrointestinal bleeding and assessment of renal and hepatic function failed to demonstrate significant differences between ibuprofen and placebo . Because a trend for reduced creatinine clearance was observed at 8 hrs in the ibuprofen group, nephrotoxicity of this drug in sepsis cannot be excluded . Temperature decreased significantly within 4 hrs of the initial dose of investigational therapy in patients who received ibuprofen (38.5 +/- 0.3 degrees to 37.0 +/- 0.2 degrees C, p less than .001) . However, despite this significant change in temperature, we were unable to detect significant differences in hemodynamic and respiratory values or survival when ibuprofen-treated patients were compared with controls . CONCLUSIONS: Ibuprofen was well tolerated when administered iv and rectally to patients with severe sepsis, although drug absorption was poor with the rectal route . Significant antipyretic effects of ibuprofen were demonstrated . Although an excellent safety profile characterized ibuprofen in this study, the absence of ibuprofen-associated toxicity may have been secondary to poor rectal absorption of the drug . Our results support the continued clinical investigation of ibuprofen in sepsis, using an all-intravenous route of administration.

J Clin Invest, 1991 Nov, 88(5), 1452 - 9
Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the sepsis syndrome; Fasano MB et al.; Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome . We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively) . There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN . Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression . In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN . Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis . Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation . Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome.

JPEN J Parenter Enteral Nutr, 1991 Nov-Dec, 15(6), 630 - 6
Histopathologic study of cholestasis induced by total parenteral nutrition or intraperitoneal sepsis in rats; Shu ZJ et al.; Wistar rats were divided into two groups, intraperitoneal sepsis group (group IS) and total parenteral nutrition group (group TPN), to evaluate the characteristics of pathologic alterations in rats with cholestasis . Biochemical assay showed that cholestasis developed in both groups after 10 days . Light microscopic examination of liver specimens revealed that the degeneration in the intermediate and external zone of hepatolobules was the major alteration in group IS, and group TPN showed characteristic dilation of central veins and hepatic sinuses and the proliferation of Kupffer cells with marked phagocytosis . Electron microscopic pictures presented the enlargement of bile canaliculi with altered microvilli in group IS and many highly electron-dense bile particles within cytoplasm and secondary lysosomes near dilated bile canaliculi in group TPN . It is concluded that there were different histopathologic alterations of liver specimens in TPN-supported animals and septic animals when cholestasis developed . It is unsuitable to take intraperitoneal sepsis as a unique factor of cholestasis in TPN-supported rats . Bile stasis is only one sign of TPN-induced hepatic lesion, which needs further exploration to determine its causes and mechanisms.

J Appl Physiol, 1991 Nov, 71(5), 1979 - 89
TNF but not IL-1 in dogs causes lethal lung injury and multiple organ dysfunction similar to human sepsis; Eichacker PQ et al.; We compared the early and late pulmonary effects of human recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) challenges in awake dogs with chronic tracheostomies . Serial blood gas analysis, bronchoalveolar lavage (BAL) with cell and protein analysis, intravascular catheter hemodynamics, and radionuclide left ventricular ejection fractions (LVEF) were determined before and after infusion of TNF (60 micrograms/kg body wt, n = 8), IL-1 (1,000 micrograms/kg body wt, n = 6), or heat-inactivated IL-1 (n = 6, controls) . Controls given heat-inactivated IL-1 had no changes (P = NS) in any pulmonary parameter throughout the study . Animals given IL-1 had a transient increase (P less than 0.05) in BAL neutrophil concentration 1 day after infusion but no other changes (P = NS) in pulmonary function throughout the study . Animals given TNF had early (0-4 h) decreases (P less than 0.05) in arterial PO2, increases (P less than 0.05) in physiological shunt fraction and alveolar-to-arterial PO2 gradient, and a high mortality rate (50%) . In TNF animals, volume challenges at 4 h were associated (P less than 0.05) with death and noncardiogenic pulmonary edema . In TNF survivors, hypoxemia persisted for 2-3 days and was associated with increases (P less than 0.05) in alveolar protein and neutrophil concentration on days 1 and 3, respectively, which in survivors returned to near normal over 6-21 days . Animals challenged with TNF and not IL-1 had reversible depression of LVEF similar in time course to abnormalities in arterial PO2 . In this study, TNF (but not IL-1) challenges were lethal and produced acute pulmonary dysfunction sustained over days (reversible in survivors) that was similar to that seen in human septic shock . The ability of TNF to induce pulmonary injury similar to bacterial shock suggests that TNF is a key mediator of sepsis-induced lung injury . Furthermore, because TNF challenge induced both sustained pulmonary and cardiac injury, TNF may be a common pathway for the multiple organ dysfunction that occurs during septic shock.

Am Surg, 1991 Oct, 57(10), 656 - 62
Patterns of liver test abnormalities in patients with surgical sepsis; Brooks GS et al.; The progression of changes in biochemical liver test results during moderate and severe sepsis (SS) was studied prospectively in 43 patients admitted to a surgical intensive care unit . Using predetermined criteria, severity of sepsis was assessed by physicians blinded to the liver test results . Linear regression analysis showed that bilirubin levels increased at a rate approximating 0.95 mg/dl/day in patients with SS, whereas alkaline phosphatase levels did not rise initially in these patients . Following peak hyperbilirubinemia, however, alkaline phosphatase levels increased at approximately 4 IU/L/day . In patients with moderate sepsis (MS), bilirubin levels increased slowly (approximately 0.4 mg/dl/day) but alkaline phosphatase levels increased rapidly (approximately 29 IU/L/day) . Following peak hyperbilirubinemia, alkaline phosphatase levels did not change . These data define patterns of liver test abnormalities of clinical importance . Rapidly rising bilirubin levels with little change in alkaline phosphatase levels are associated with SS, whereas markedly elevated alkaline phosphatase levels may indicate MS or resolution of SS . In critically ill surgical patients subjected to many potential hepatic insults, recognition of liver dysfunction with these patterns should alert the clinician to the possibility of underlying sepsis.

Br J Surg, 1991 Oct, 78(10), 1187 - 8
Subareolar dissection for duct ectasia and periareolar sepsis; Hartley MN et al.; Excision of the major duct system of the breast for symptoms owing to mammary duct ectasia may be curative, but recent reports have been less optimistic . A retrospective study (1978-1990) of 46 women (median age 38 years, range 18-78 years) who underwent subareolar dissection with antibiotic cover for symptoms associated with duct ectasia is presented . Thirty-three women presented without symptoms of overt sepsis (periareolar lump, nipple discharge or nipple retraction) . Following subareolar dissection, six developed recurrent symptoms and five required further surgery . Thirteen women presented initially with abscesses . Eight abscesses recurred following incision and drainage, and one developed a mammillary fistula . Following subareolar dissection, six developed recurrent sepsis requiring further surgery.

Am Surg, 1991 Oct, 57(10), 618 - 23
Prevention of central venous catheter sepsis: a prospective randomized trial; Bonawitz SC et al.; A prospective randomized trial was undertaken to evaluate the influence of routine 72-hour catheter exchange and the use of an implantable collagen cuff in preventing central venous catheter infection in critically ill patients requiring multiple lumen central venous access . Patients were randomized to one of four groups, which determined whether the central venous catheter placed would be removed at 3 or 7 days and whether an implantable collagen cuff would be used or not . Upon removal, cultures of the central line tip, the insertion site, and peripheral blood were obtained . One hundred and fifty-nine catheters were studied in 85 patients during a 14-month period . There were 26 (16.4%) episodes of catheter colonization and four (2.5%) episodes of catheter infection in the entire population . Catheter colonization rates (same organisms cultured from catheter tip and skin site) were 14.5 per cent at 3 days and 18.4 per cent at 7 days . Infection rates (same organism cultured from catheter tip and peripheral blood culture) were 2.4 per cent at 3 days and 2.6 per cent at 7 days . With regard to the use of the collagen cuff, colonization rates were 14.5 per cent with the use of the cuff and 18.1 per cent without the use of the cuff . Infection rates were 5.3 per cent with the use of the cuff and 0 per cent without the use of the cuff . None of these differences reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Physiol, 1991 Oct, 261(4 Pt 2), R965 - 72
Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker {18F}fluoromisonidazole; Hotchkiss RS et al.; Underlying cellular hypoxia, which may be difficult to detect, has been postulated to be a major cause of morbidity and mortality in sepsis . We employed the novel hypoxic marker {18F}fluoromisonidazole to determine whether cellular hypoxia was present in a peritonitis model of sepsis in the rat . A second group of septic and control rats had organ blood flow measurements determined by the radiolabeled microsphere technique to relate possible ischemia to decreased organ perfusion . No evidence of cellular hypoxia was detected in skeletal muscle, brain, liver, heart, or diaphragm in the septic rats . Ligation of the femoral artery caused a greater reduction in flow (55% decrease vs . 20% decrease, P less than 0.05) and an increased retention of {18F}fluoromisonidazole in skeletal muscle of the septic rats . We conclude that sepsis does not invariably result in systemic, i.e., multiorgan, cellular hypoxia and that underlying cellular hypoxia is not the major pathophysiological abnormality in sepsis . The greater reduction in muscle blood flow and the increased retention of {18F}fluoromisonidazole in the ischemic muscle of septic rats implies that they may be more vulnerable to hypoxia.

Circ Shock, 1991 Oct, 35(2), 65 - 77
Imbalance between plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha during subacute endotoxin-induced hyperdynamic sepsis or multiple organ failure syndrome in sheep; Pittet JF et al.; We compared the time course of plasma and pulmonary lymph levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin (PG)F1 alpha during the development of either the hyperdynamic phase of sepsis or of the multiple organ failure syndrome (MOFS) associated with sepsis in 26 chronically instrumented awake sheep with intravascular catheters and a chronic pulmonary lymph fistula . Using a continuous i.v . infusion of Escherichia coli endotoxin administered at a rate of 20 ng.kg-1.min-1 (group E20, n = 9) resulted in hyperdynamic septic shock with more than 75% of animals surviving after 72 h of continuous endotoxin administration . Infusing endotoxin at a higher dosage (40 ng.kg-1.min-1; group E40, n = 9) resulted in the development of respiratory failure and MOFS with death occurring within 55 hr of endotoxemia . Eight similarly instrumented sheep served as controls . Administration of endotoxin produced within 4 hr in both endotoxin groups a significant increase in arterial plasma concentration of TxB2, which was not significantly different between both endotoxin groups . Thereafter, plasma TxB2 concentrations progressively decreased in the E20 group to reach at 36 hr values significantly lower than those measured in control sheep not given endotoxin . In the E40 group, plasma TxB2 concentrations returned to baseline values during the development of a MOFS . The time course of TxB2 concentrations in pulmonary lymph in both endotoxin groups was similar to that measured in each group in plasma . 6-Keto-PGF1 alpha concentrations in arterial plasma and pulmonary lymph were significantly higher than in controls during the first 20 hr following the start of endotoxin infusion in both endotoxin groups and were not different between these groups . Thereafter, plasma and pulmonary lymph 6-keto-PGF1 alpha concentrations progressively returned to baseline values in the E20 group and remained at these levels up to the end of the study period (72 hr) . In the E40 group, plasma 6-keto-PGF1 alpha concentrations also decreased to baseline values during the second day of endotoxemia but then significantly increased in sheep that survived more than 36 hr and developed a hypodynamic septic state . During the first 24 hr of endotoxemia, the plasma TxB2/6-keto-PGF1 alpha ratio was similar in controls and in both endotoxin groups . During the second study day, TxB2/6-keto-PGF1 alpha ratio progressively decreased in both endotoxin groups to reach and maintain values significantly lower than those measured in controls at 36 hr in the E40 group and at 52 hr in E20 group.(ABSTRACT TRUNCATED AT 400 WORDS)

Inflammation, 1991 Oct, 15(5), 355 - 67
Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis; Green JA et al.; Elevation of circulating phospholipase A2 (PLA2) activity is associated with sepsis and septic shock . Elevated levels of PLA2 activity also are seen in association with chronic inflammatory disorders such as rheumatoid arthritis . The relationship between these phospholipases is unclear . We have developed a highly specific enzyme-linked immunosorbent assay (ELISA) capable of measuring human synovial PLA2 in plasma, using monoclonal antibodies raised to recombinant synovial PLA2 . This ELISA has been used to quantitate circulating PLA2 levels in patients clinically diagnosed with sepsis . These elevated levels positively correlated with the elevation seen in plasma PLA2 enzyme activity . The antibodies also have been used to purify immunoreactive PLA2 from plasma of patients with sepsis, thus enabling characterization of the purified protein by amino-terminal sequence analysis . We conclude from this study that the increase in PLA2 activity seen in association with sepsis and septic shock results from a dramatic elevation in levels of a circulating PLA2 enzyme . This inflammatory PLA2 is indistinguishable, both immunologically and chemically, from that associated with rheumatoid arthritis . Therapeutic agents directed towards inhibition of this inflammatory PLA2 enzyme may have utility in the treatment of both chronic and acute inflammatory disease.

Indian Pediatr, 1991 Oct, 28(10), 1159 - 64
Diagnostic and prognostic utility of C-reactive protein, alpha-1-antitrypsin and alpha-2-macroglobulin in neonatal sepsis: a comparative account; Suri M et al.; C-reactive protein (CRP), alpha-1-antitrypsin (alpha-1-AT) and alpha-2-macroglobulin (alpha-2-MG) levels were evaluated serially in 25 healthy and 20 septicemic neonates and then compared as early diagnostic aids and prognostic indicators in this illness . Compared to healthy controls, septicemic neonates had significantly higher mean CRP levels (p less than 0.01) . Neonates with septicemia, who recovered, had higher mean CRP levels than the group which died (p less than 0.05) . As an early diagnostic aid CRP had a low Youden index, whereas for prognosis its index was higher . Septicemic neonates also had significantly higher mean alpha-1-AT levels (p less than 0.05), 12-24 hours after onset of illness, as compared to healthy neonates . Alpha-1-antitrypsin could not be used as an early diagnostic aid in septicemia, but was useful for predicting outcome . Mean alpha-2-macroglobulin levels did not show significant variation in healthy and septicemic neonates . Lower mean alpha-2-MG levels were observed in neonates recovering from septicemia . As an early diagnostic aid alpha-2-MG had a low Youden index, whereas for prognosis its index was higher . CRP had a higher Youden index than alpha-2-MG for early diagnosis of neonatal septicemia and had a higher index than both alpha-1-AT and alpha-2-MG for predicting outcome in septicemia . Serial use of CRP alone is, therefore, recommended for both purposes.

Jpn J Clin Oncol, 1991 Oct, 21(5), 353 - 9
The frequency and management of infectious episodes and sepsis in small cell lung cancer patients receiving intensive chemotherapy with granulocyte-colony stimulating factor; Oshita F et al.; The relation between degree of myelosuppression and episodes of infection was analyzed in 36 patients (92 treatment courses) with small cell lung cancer (SCLC) treated with intensive chemotherapy . The two regimens used were cisplatin (CDDP) + adriamycin (ADR) + cyclophosphamide (CPA) + etoposide (VP-16) + granulocyte-colony stimulating factor (G-CSF) and CDDP + teniposide (VM-26) + G-CSF, and they induced grade 3 or 4 leukopenia in 88% of treatment courses and febrile episodes in 60% . In the febrile courses, the mean nadirs of leukocyte and neutrophils (820 +/- 581/mm3, 101 +/- 267/mm3) were significantly longer (P less than 0.01) and the mean durations of grade 3 and 4 leukopenia and neutropenia significantly longer (P less than 0.001) than those of the non-febrile courses . It was noted, however, that febrile episodes appeared frequently in courses having the nadir of leukocytes below 1,000/mm3 (80%) or the nadir of neutrophils below 100/mm3 (74%) . The administration of antibiotics was required for about 7 days to patients with febrile episodes . Sepsis was experienced in five courses, in which the neutrophils were all zero . All the patients, however, could be managed by an administration of antibiotics immediately after a febrile episode appeared, without delaying the subsequent chemotherapy except for one patient, who had had a performance status (PS) of 3 prior to chemotherapy.

Schweiz Med Wochenschr, 1991 Sep 21, 121(38), 1387 - 92
{Tumoral calcinosis with superinfection and sepsis}; Oeggerli P et al.; Tumoral calcinosis (TC) is a rare syndrome involving ectopic calcifications in the vicinity of the large joints . In about one third of patients the disorder is familial and is associated with hyperphosphatemia, elevation of 1,25-dihydroxy-vitamin-D levels and peculiar dental lesion . TC is inherited in an autosomal-recessive manner . In a normophosphatemic male patient with alcoholic cirrhosis of the liver, TC occurred first in the thoracic wall . Seven years after excision of the first lesion, a large tumor mass around the right hip developed . Infection of the calcified masses with Staph . aureus led to extensive abscess formation, septicemia and death at the age of 64 . Clinical, dental and biochemical examination of the 7 descendants of the patient revealed no constitutional signs of the disease, thus identifying our patient as a sporadic case . Clinical and pathological findings in the patient are discussed and the literature is reviewed.

Ann Intern Med, 1991 Sep 15, 115(6), 457 - 69
The pathogenesis of sepsis; Bone RC; Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses . Many mediators of the pathogenesis of sepsis have recently been described . These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade . Neutrophil and platelet activation may also play a role . Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins . Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other . A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role . Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design . Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators . Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8 . Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults . Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response.

Baillieres Clin Gastroenterol, 1991 Sep, 5(3 Pt 1), 611 - 37
Intra-abdominal sepsis: the role of surgery; Gallinaro RN et al.; The role of the surgeon in intra-abdominal sepsis is multifactorial . A comprehensive understanding of the incidence and pathophysiology of diseases which cause intra-abdominal sepsis is the key to the diagnosis and treatment of such ailments . In simplest terms, the aetiology has two basic mechanisms: (a) violation of the 'bug-body barrier' and (b) obstruction to the flow of a body fluid with subsequent bacterial overgrowth . Either of these mechanisms may affect any of the organs within the abdomen, leading to sepsis . The peritoneal cavity is a dynamic structure which responds to insults in certain predictable manners which notify the alert physician that danger is present . Recognition of these signs through history and physical examination are the most important aspects of diagnosis . Confirmation of suspicions can be obtained with radiological modalities, but they are not a substitute for clinical judgement . Treatment of intra-abdominal sepsis should always begin with resuscitation and systemic antibiotics . Alleviation of the septic source is mandatory, and this may be achieved either operatively or non-operatively (i.e . percutaneous or endoscopic procedures) . When the patient does not improve after the initial procedure, then a missed focus of infection must be investigated . In some cases, a planned or staged second operation may be needed to further debride necrotic tissue . Antibiotics should be of adequate spectrum and bioavailability to kill the species of bacteria most likely to cause the infection . This regimen may be altered when culture and sensitivity reports are completed . Finally, patients whose immune system function has been altered by disease or treatment must be assumed very ill until proven otherwise . These are general guidelines in the management of patients with intra-abdominal sepsis . Individual cases may necessitate slight modifications, but all require a high level of vigilance and expertise in order to combat a very lethal disease.

Midwifery, 1991 Sep, 7(3), 102 - 6
Puerperal sepsis: its contribution to maternal mortality; Kwast BE; Puerperal sepsis is the second most common cause of maternal mortality in the developing world . In this paper the extent of the problem is described and factors affecting puerperal sepsis are identified . Methods of reducing the incidence of puerperal sepsis are suggested . This paper is based on one originally given at the ICM/WHO/UNICEF pre-congress workshop in Kobe, Japan, October, 1990.

Br J Surg, 1991 Sep, 78(9), 1031 - 8
Postsplenectomy sepsis and its mortality rate: actual versus perceived risks; Holdsworth RJ et al.; A collective critical review of the literature on postsplenectomy sepsis from 1952 to 1987 has been undertaken . The reports cover a cohort of 12,514 patients undergoing splenectomy but of these only 5902 reports were sufficiently detailed to allow a useful analysis . The incidence of infection after splenectomy in children under 16 years old was 4.4 per cent with a mortality rate of 2.2 per cent . The corresponding figures for adults were 0.9 per cent and 0.8 per cent respectively . The present analysis of well documented patients has shown that severe infection after splenectomy for benign disease is very uncommon except in infants (infection rate 15.7 per cent) and children below the age of 5 years (infection rate 10.4 per cent) . Many of these reported postsplenectomy infections may have been coincidental . It is also apparent that children contract a different type of infection after splenectomy than adults, predominantly a meningitis which is less frequently fatal . Adults, in contrast, appear to develop a septicaemic type of illness associated with a higher mortality rate . This survey has also shown that children are reported to be more susceptible to pneumococcal sepsis than to infection caused by any other organism . Although the removal of the spleen in otherwise normal people does not appear to be associated with an increased frequency of infection, the presence of a coexistent disorder, notably hepatic disease, can increase the risk substantially.

Baillieres Clin Gastroenterol, 1991 Sep, 5(3 Pt 1), 587 - 609
Intra-abdominal sepsis: the role of radiology; Adam EJ et al.; A wide range of imaging tools is available for the investigation of abdominal sepsis . Plain films and barium studies alone are generally regarded as inadequate and most patients will require ultrasound, CT or nuclear medicine studies to locate the source of sepsis . The choice of imaging modality depends on several factors, most important of which are the clinical condition of the patient and the presence or absence of localizing signs and symptoms . Ultrasound has the advantage of being portable and is therefore probably the best initial imaging method for the critically ill patient . It should also be the first investigation in patients with signs and symptoms localizing to the right upper quadrant, renal areas, subphrenic spaces or pelvis . Transvaginal ultrasound is particularly useful in examining the pelvis . CT is the imaging modality of choice for the pancreas and retroperitoneum and in patients who are poor candidates for ultrasound or in whom visualization on ultrasound is inadequate . In patients with PUO or evidence of sepsis without localizing signs or symptoms, nuclear medicine studies in the form of 67Ga citrate or labelled white cell scans are useful to localize the septic focus, although in most cases CT or ultrasound will subsequently be required for detailed anatomical definition . Imaging techniques have an increasingly important role to play in the treatment of sepsis, and guided aspiration and drainage may be performed with a high degree of accuracy under ultrasound or CT guidance, eliminating the need for surgical intervention in many individuals.

Pediatr Infect Dis J, 1991 Sep, 10(9), 663 - 8
Diminished IgG, but not complement C3 or C4 or factor B, precedes nosocomial bacterial sepsis in very low birth weight neonates; Lassiter HA et al.; The significance of low serum IgG and complement proteins in very low birth weight (VLBW; less than 1500 g) neonates is not known . Therefore serum IgG, C3, C4 and Factor B were quantitated weekly by rate nephelometry in 15 VLBW neonates who developed proven nosocomial bacterial or candidal sepsis (Group A) and 27 VLBW neonates who did not develop sepsis (Group B) . In the first week of life the serum IgG of neonates in Group A was 295 +/- 33 mg/dl (mean +/- SEM) and in Group B it was 440 +/- 21 mg/dl (P less than 0.01) . In the second week, the IgG of Group A was 270 +/- 32 mg/dl and that of Group B was 473 +/- 38 mg/dl (P less than 0.01) . If the IgG was less than 350 mg/dl in the first week or less than 230 mg/dl in the second week, the relative risk of acquiring sepsis was greater than or equal to 5 (95% confidence interval in the first week, 1.7 to 11.2) . The serum IgG was measured before the onset of sepsis in 14 of the 15 neonates in Group A . In the week before sepsis the IgG of the 14 neonates was less than 440 mg/dl (range, 45 to 433 mg/dl) in all cases, was below the mean IgG of Group B in 12 of 14 cases (P = 0.006 vs . Group B) and was greater than 2 SD below the mean IgG of Group B in 4 of 14 cases (P = 0.0003 vs . Group B).(ABSTRACT TRUNCATED AT 250 WORDS)

J Bone Joint Surg Br, 1991 Sep, 73(5), 783 - 6
Total arthroplasty of the hip after childhood sepsis; Kim YH; Total hip arthroplasty was performed in 45 hips of 44 patients who had pyogenic arthritis of the hip during childhood . The average age of the patients was 36.4 years (range 19 to 50) . The interval between active infection and arthroplasty ranged from 11 to 40 years, and average follow-up was 65.4 months (range 58 to 80) . Specimens of tissue taken before and during operation gave negative cultures in all hips, and no patient had reactivation of infection . The mean functional rating of the hips was 58 points before operation and 90 at the final review . Complications were seen in 11 cases (24%), loosening of components occurred in six (13%) and one hip had to be revised for acetabular component migration . Acetabular allografts were required in 27 hips (60%) . All allografts united but there was partial resorption of the graft in the non-weight-bearing area in all.

Eur J Immunol, 1991 Sep, 21(9), 2177 - 84
Dissociation between plasma and monocyte-associated cytokines during sepsis; Munoz C et al.; We report our investigations of circulating interleukin (IL) 1 beta, IL 6 and tumor necrosis factor (TNF)-alpha, as well as cell-associated IL 1 alpha, IL 1 beta and TNF-alpha in plasma and monocytes of 21 patients with sepsis syndrome and 6 patients with non-septic shock . Longitudinal studies reveal that (a) the most frequent detectable plasma cytokines were TNF-alpha and IL 6, (b) the presence and the kinetics of circulating cytokines were independent of one other, (c) detectable levels of cytokines could be found for a long period of time, and (d) significantly higher levels of IL 6 were found for non-surviving patients . Because of the in vivo half-life of cytokines and of the existence of numerous specific high-affinity receptors, it is quite probable that detectable plasma cytokines represent the excess of produced mediators which have not been trapped by the target cells . TNF-alpha (410 +/- 65 pg/10(6) monocytes) and IL 1 beta (153 +/- 60 pg/10(6) monocytes) were frequently found associated to monocyte lysates (88% and 50%, respectively) . Despite the fact that IL 1 alpha is the most abundant cytokine found associated to monocytes following in vitro activation, IL 1 alpha was rarely found in monocytes of intensive care unit patients (29%) . No correlation was found to exist between the levels of plasma cytokines and cell-associated cytokines . Some patients had plasma TNF-alpha or IL 1 beta in the absence of the corresponding monocyte-associated cytokine . This observation suggests that cells other than monocytes can participate in the production of circulating cytokines . At the end of the longitudinal study (day 14 +/- 2), only 2/12 surviving patients still had plasma TNF-alpha, whereas 8/12 had monocyte-associated TNF-alpha . These results indicate that activation of monocytes still occurs in patients for whom no plasma cytokines can be detected . Thus, in addition to the measurement of plasma cytokine, measurement of cell-associated cytokine appears useful to assess cytokine production and monocyte activation in vivo.

Crit Care Med, 1991 Sep, 19(9), 1114 - 9
Differential detection of plasma hydroperoxides in sepsis; Keen RR et al.; OBJECTIVE: To determine whether plasma lipid hydroperoxides may be a useful marker for sepsis . DESIGN: Exploratory, open-label study . SETTING: Critical care unit at a university medical center . PATIENTS: Twelve patients with sepsis syndrome requiring hemodynamic monitoring with pulmonary artery catheters . Seven patients were diagnosed with pulmonary infections and five patients had intra-abdominal infections . INTERVENTIONS: Fatty acid hydroperoxide was measured in the fresh arterial plasma (radial artery) and mixed venous plasma (pulmonary artery) from each patient . Hydroperoxide was determined using a sensitive assay based on activating the cyclooxygenase reaction of prostaglandin H synthase . MEASUREMENTS AND MAIN RESULTS: The mean difference between the amount of fatty acid hydroperoxide measured in the plasma draining involved regions (arterial plasma for pulmonary sepsis, mixed venous plasma for intra-abdominal sepsis) compared with the paired, uninvolved regions was 0.45 +/- 0.14 microM (mean +/- SEM; p less than .005) . CONCLUSIONS: Increased lipid hydroperoxides in blood-draining septic foci are markers of oxyradical release associated with severe infection, although they are not specific for infectious conditions, being released also from nonseptic regions of surgical trauma . Assays for hydroperoxides may be useful when relatively free of other tissue trauma.

Anesth Analg, 1991 Sep, 73(3), 289 - 94
Is dantrolene safe to administer in sepsis? The effect of dantrolene after endotoxin administration in dogs and rats; Beebe DS et al.; Hyperthermia from septic shock may be indistinguishable from malignant hyperthermia . Dantrolene may be given in septicemia if the diagnosis is unclear . To determine if dantrolene is safe to use in sepsis, two studies were performed . In study 1, 18 anesthetized dogs in which profound septic shock was induced with 5 mg/kg of intravenous Escherichia coli endotoxin were randomized to receive (30 min later) intravenous injections of 10 mg/kg of dantrolene solution, the diluent of dantrolene, or maintenance intravenous fluids alone . The use of dantrolene solution and the diluent of dantrolene resulted in similar but transient statistically significant increases in the cardiac filling pressures and cardiac outputs and decreases in the vascular resistances compared with the control dogs . In a second study, 185 rats were randomized into five equal groups . Groups 1, 2, and 3 received 15 mg/kg of intraperitoneal Escherichia coli endotoxin followed 30 min later by 10 mg/kg of dantrolene solution, the diluent of dantrolene, or normal saline . Groups 4 and 5 received normal saline followed by dantrolene or normal saline . The survival of groups 1, 2, and 3 was less at 24 h (P less than 0.0001) than that of either control group, but was not significantly different from one another . The results suggest dantrolene can be administered safely under clinical conditions where the cause of hyperthermia and shock cannot clearly be ascribed to malignant hyperthermia or septicemia.

Indian J Pediatr, 1991 Sep-Oct, 58(5), 661 - 4
Neonatal sepsis due to vertical transmission from maternal genital tract; Ayengar V et al.; High vaginal swabs (HVS) of 1792 expectant mothers were sent for culture at the time of delivery, prior to first vaginal examination . The newborns were followed-up for development of superficial or deep infections . Appropriate cultures of the babies who developed infections were sent . Bacterial growth of predominantly gram-ve organisms was obtained in 1026 (57%) HVS . Infection developed in 48 (27%) babies in 1st 72 hours of life, of which 28 had deep infection while the rest had superficial infection . Vertical transmission of organisms was documented in 24 (1.3%) mother-baby dyads and the same was 72% in newborns who were at risk of developing sepsis by septicemia scoring, showing a significantly higher incidence of vertical transmission and subsequent sepsis in high risk newborns.

Infection, 1991 Sep-Oct, 19(5), 317 - 23
Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock; Boekstegers P et al.; In 40 intensive care patients, tissue oxygen partial pressure distribution within skeletal muscle was measured in order to estimate peripheral oxygen availability . In septic patients with multiple organ failure (n = 20) mean skeletal muscle pO2 was abnormally high (48.8 +/- 8.5 mmHg, p less than 0.001) in contrast to patients with limited infection without sepsis (28.3 +/- 5.9 mmHg, n = 10) . Mean muscle pO2 also discriminated between septic and cardiogenic shock (22.6 +/- 6.9 mmHg, p less than 0.001) . The characteristic pattern of oxygen availability in septic patients--but not in patients with limited infection--was high skeletal muscle pO2 high whole body oxygen delivery and low whole body oxygen extraction, which was not influenced by the type of pathogenic agent of sepsis . In our patients in severe stage of sepsis, we did not observe local skeletal muscle hypoxia due to microcirculatory disorder . High mean skeletal muscle pO2 suggested reduced oxygen consumption within tissue rather than reduced oxygen transport to tissue in sepsis.

Anesteziol Reanimatol, 1991 Sep-Oct, (5), 32 - 4
{Changes in the amino acid spectrum of the blood in patients with sepsis in the process of complex intensive therapy}; Spas VV et al.; Amino acid fund has been studied during complex therapy of 25 patients with sepsis . In 15 patients complex therapy included detoxicating hemosorption (3-5 sessions), in 10 patients hemosorption was supplemented by ultraviolet blood irradiation (5-10 sessions) . Complex therapy employing hemosorption led to a decrease in serine plasma level . Changes in the amino acid fund of the whole blood were insignificant . Leucine, isoleucine, threonine and phenylalanine blood levels were significantly increased . The introduction of ultraviolet blood irradiation into complex therapy of patients reduced traumatic effect of sorption detoxication on blood cells and enhanced detoxicating effect.

J Surg Res, 1991 Aug, 51(2), 158 - 64
Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage; Meldrum DR et al.; Various beneficial effects of calcium channel blockers on cell and organ function following endotoxic shock, organ ischemia, and reperfusion have been reported; however, it is not known whether these agents have any salutary or deleterious effects on immune responses after low-flow conditions . Therefore, the aim of this study was to determine (a) the effect of hemorrhage on lymphocyte IL-2, IL-3, IL-6, and IFN-gamma synthesis, and (b) whether diltiazem has any salutary or adverse effects on these parameters when administered following hemorrhage and resuscitation . To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg, maintained at that level for 60 min, and resuscitated with shed blood plus twice that volume of Ringer's lactate . Immediately following resuscitation mice received either diltiazem (2400, 800, or 400 micrograms/kg body wt), or an equivalent volume of saline . The mice were sacrificed 24 hr later, splenic lymphocytes were obtained, and their capacity to produce lymphokines was assessed . The results indicated that in the vehicle-treated animals, hemorrhage significantly decreased (P less than 0.05) IL-2, IL-3, IL-6, and IFN-gamma synthesis by 82 +/- 19%, 64 +/- 28%, 71 +/- 11%, and 86 +/- 14%, respectively . However, diltiazem (400 but not 2400 micrograms/kg) treatment after hemorrhage restored lymphocyte capacity to produce IL-2, IL-3, IL-6, and IFN-gamma (P less than 0.05) . Additional groups of animals were subjected to sepsis by cecal ligation and puncture 3 days following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Surg, 1991 Aug, 214(2), 141 - 8
The complex pattern of cytokines in sepsis . Association between prostaglandins, cachectin, and interleukins; Ertel W et al.; Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis . Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p less than 0.05) of plasma TNF until 10 hours, steadily increasing (p less than 0.05) IL-1 plasma levels, and enhanced (p less than 0.05) IL-6 plasma levels at all time points compared to the sham group . Prostaglandin E2 plasma levels were elevated (p less than 0.05) at 5 hours (153 +/- 29 pg/mL; control: 47 +/- 11 pg/mL) and 10 hours (96 +/- 16 pg/mL; control: 21 +/- 5 pg/mL) . Prostaglandin E2 production by splenic macrophages (sM phi) from septic animals was increased (p less than 0.05) at 5 hours (9.1 +/- 2.2 ng/mL) and 10 hours (5.6 +/- 1.5 ng/mL) compared to controls (3.3 +/- 0.3 ng/mL at 5 hours; 1.3 +/- 1.3 ng/mL at 10 hours) . Incubation of sM phi from septic animals with ibuprofen enhanced (p less than 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p less than 0.05) . These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis.

Surg Clin North Am, 1991 Aug, 71(4), 749 - 64
Sepsis . What it is and how to recognize it; Mileski WJ; Sepsis, shock, and resuscitation may result in various degrees of ischemia-perfusion injury that may produce widespread organ dysfunction through complex interactions and activation of host immunoinflammatory processes . As the pathophysiologic mechanisms of the inflammatory response are better defined, we may be able to modulate the generalized inflammatory state we know as sepsis and prevent the development of multiple organ failure syndrome . At present, however, the mainstay of therapy remains prompt resuscitation to eliminate regions of hypoperfusion and to limit as much as possible those factors that predispose to further organ injury while the source of inflammatory stimulation is being identified and controlled.

Crit Care Med, 1991 Aug, 19(8), 1060 - 6
Reduced alveolar macrophage production of tumor necrosis factor during sepsis in mice and men; Simpson SQ et al.; BACKGROUND AND METHODS: Tumor necrosis factor (TNF) has been implicated as a major humoral mediator of sepsis and endotoxin shock . TNF is secreted by cells of the reticuloendothelial system, including alveolar macrophages . Alveolar macrophage TNF production has been postulated to play a pathogenetic role in the development of adult respiratory distress syndrome (ARDS) in sepsis . To evaluate alveolar macrophage production of TNF during sepsis and endotoxin shock, we studied the effects of sepsis and/or in vivo lipopolysaccharide on the in vitro production of TNF by pulmonary alveolar macrophages . Human pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from six septic and five nonseptic patients, cultured in the presence or absence of lipopolysaccharide (1 ng/mL), and assayed for TNF activity in a bioassay using fibroblast lysis . A murine model of sepsis was also utilized to study pulmonary alveolar macrophage TNF production under more controlled conditions . Normal mice were given ip injections of either lipopolysaccharide or saline . After 2 hrs, pulmonary alveolar macrophages were obtained and cultured in saline or various concentrations of lipopolysaccharide (0.001 to 10 micrograms/mL) . RESULTS: There was no difference in baseline TNF activity, expressed as per cent lysis at 1:10 dilution, between pulmonary alveolar macrophages from control and septic patients (35.7 +/- 5.5% vs . 24.4 +/- 9.3%, respectively) (p greater than .05) . However, when stimulated with lipopolysaccharide in vitro, the pulmonary alveolar macrophages from nonseptic patients produced significantly (p less than .01) more TNF (82.8 +/- 3.6%) than did pulmonary alveolar macrophages from patients with the septic syndrome (35.2 +/- 3.8%) . Similar findings were obtained using the murine sepsis model . The baseline TNF activity in pulmonary alveolar macrophages from control mice was 22.9 +/- 7.0% (mean +/- SEM) and from lipopolysaccharide-injected mice was 26.8 +/- 3.3% (p greater than .05) . Stimulation with 1 ng/mL lipopolysaccharide in vitro produced an increase in TNF activity in both groups, but the increase was greater in the control mice (68.1 +/- 5.7%) than in the lipopolysaccharide-injected mice (47.5 +/- 5.3%) (p less than .01) . When the murine pulmonary alveolar macrophages were stimulated with higher concentrations of lipopolysaccharide (0.1 to 10 micrograms/mL), pulmonary alveolar macrophages from lipopolysaccharide-injected mice produced less than 25.5% of the TNF produced by pulmonary alveolar macrophages from control mice . CONCLUSIONS: These studies indicate that sepsis and endotoxin injection result in a rapid decrease in the ability of pulmonary alveolar macrophages from both humans and mice to produce and secrete TNF in response to lipopolysaccharide . We speculate that a downregulation of TNF production or of macrophage responsiveness to lipopolysaccharide has occurred . These results suggest that sustained TNF production by macrophages is not required for lung injury in sepsis.

Zhonghua Nei Ke Za Zhi, 1991 Aug, 30(8), 484 - 6, 521
{Bacterial sepsis and nosocomial infection: a study of 70 patients}; Deng GH et al.; 74 episodes of bacterial sepsis in 70 patients were analysed from July 1988 to June 1989 . The incidence of sepsis is 0.7% of the whole admitted patients . Compared to a similar previous study from April 1982 to March 1983, the incidence of sepsis decreased (P less than 0.01), and the incidence of nosocomial sepsis remained unchanged, whereas its mortality decreased (P less than 0.05) . The host defenses are important in predisposing to sepsis and determining prognosis . Antibiotic sensitivity test revealed that some bacterial strains were resistant to new beta-lactam antibiotics.

Am J Physiol, 1991 Aug, 261(2 Pt 1), G287 - 94
Increased glucose uptake by intestinal mucosa and muscularis in hypermetabolic sepsis; Lang CH et al.; The purpose of the present study was to determine the following: 1) whether the sepsis-induced increase in glucose uptake was a generalized response along the entire length of the gastrointestinal tract; 2) the relative contribution of the mucosa and muscularis to the enhanced uptake; and 3) whether reducing intestinal blood flow would attenuate the elevated rate of glucose uptake . Hypermetabolic sepsis increased in vivo glucose uptake in all sections of the gastrointestinal tract (57-93%) except the stomach . The rates of glucose uptake per gram of tissue by the mucosa and muscularis were not different . However, because the mucosa accounted for the majority of the whole intestine mass, this layer was responsible for 76-78% of the glucose uptake by the entire small intestine . Intestinal blood flow, determined with the use of radiolabeled microspheres, increased by 127% in sepsis . In both groups, approximately 70% of the total intestinal blood flow was distributed to the mucosa . Somatostatin was infused to produce splanchnic vasoconstriction and decreased the sepsis-induced increment in intestinal flow to the mucosa and muscularis (38 and 54%), whereas the enhanced rate of glucose uptake was not altered . Somatostatin also produced a severe insulinopenia . These results indicate that hypermetabolic sepsis increases glucose uptake to a similar extent along the length of the small and large intestine and that the majority of this increase is due to an enhanced uptake by the mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Circ Shock, 1991 Aug, 34(4), 356 - 63
Intraabdominal sepsis: enhanced autooxidative effect on polymorphonuclear leukocyte cell surface receptor expression; Simms HH et al.; We investigated the effects of untreated intraabdominal sepsis on the interrelationship between PMN oxidative metabolism and cell surface receptor expression . Female swine underwent either sham laparotomy (n = 7) or cecal ligation and incision (n = 9) with assays conducted on postoperative days (POD) 0, 1, 4, and 8 . Superoxide anion production, intracellular H2O2 production, and the cell surface expression of Fc gamma RII, III, CR1, and CR3 were measured . In addition, phagocytosis of serum-opsonized zymosan was used as a multivalent ligand for CR3 and subsequently Fc gamma RII, III, and CR1 expression were assayed to determine if intraabdominal sepsis induces a linkage between complement and Fc gamma receptor expression . Superoxide anion production increased between POD 0 and 4 and fell between POD 4 and 8 in animals with untreated intraabdominal sepsis . Intracellular H2O2 production rose between POD 0 and 1 and then fell progressively in animals with untreated intraabdominal sepsis . Simulation of the oxidative burst using glucose/glucose oxidase reduced Fc gamma RII and III expression in both sets of animals with a greater reduction seen by POD 4 in animals with intraabdominal sepsis . CR1/CR3 expression was increased with glucose/glucose oxidase by POD 4 in the presence of intraabdominal sepsis . Xanthine/xanthine oxidase did not alter cell surface receptor expression . Phagocytosis of serum-opsonized zymosan decreased subsequent Fc gamma RII expression in animals with intraabdominal sepsis by POD 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Surg, 1991 Aug, 78(8), 961 - 3
Gallbladder sepsis after stent insertion for bile duct obstruction: management by percutaneous cholecystostomy; Ainley CC et al.; Of 364 patients undergoing insertion of a biliary endoprosthesis in 1989, six (1.6 per cent) developed gallbladder sepsis . Three patients had cholangiocarcinoma, two had carcinoma of the pancreas and one had a benign biliary stricture . Two of the five patients with malignancy had gallbladder stones, and the patient with a benign stricture developed stones after 3 years of stenting . Three patients developed gallbladder sepsis early after endoprosthesis insertion (less than 6 days), while in the other three it occurred late (greater than 6 months) . All six patients failed to respond to antibiotics and were successfully managed by percutaneous cholecystostomy; the patient with a benign biliary stricture also had cholecystolithotomy . The gallbladder drainage tubes were removed or became dislodged at intervals varying from 2 weeks to 6 months without complications . Percutaneous cholecystostomy is the treatment of choice for gallbladder sepsis unresponsive to antibiotics in patients with a biliary endoprosthesis in situ.

Surgery, 1991 Aug, 110(2), 318 - 25; 325-6
Sepsis alters skeletal muscle energetics and membrane function; Jacobs DO et al.; The effects of sepsis on skeletal muscle energetics and membrane function are poorly understood, and the time course of changes in energy metabolism are unclear . To clarify these relationships, high energy phosphate ratios, intracellular pH, and phosphocreatine breakdown rates were measured in vivo in the gastrocnemius muscle of adult male Wistar rats after cecal ligation and puncture or sham operation with 31P magnetic resonance spectroscopy . Adenosine triphosphate (ATP) concentration and Na(+)-K+ ATPase and creatine kinase activities were determined in vitro . Within 24 hours, Na(+)-K+ ATPase activity increased by 60% in rats with cecal ligation and puncture, all of which had positive bacterial cultures, as compared to none of the sham-operated controls . Phosphocreatine/ATP ratios decreased by 20% in association with a quantitatively similar increase in phosphocreatine breakdown (9.7 +/- 0.5 vs 11.9 +/- 0.5 mumoles/gm wet wt/sec; p = 0.01) . ATP concentrations were maintained, and intracellular pH did not change significantly . In this model, changes in phosphocreatine breakdown were not related to total creatine kinase activity, which did not change significantly, or increases in adenosine 5'-diphosphate (ADP) concentration (62 +/- 8 vs 92 +/- 8 mumols/L; p = 0.02) . Thus, in early sepsis before a measurable decrease in pH occurs, ATP is utilized at an increased rate to help maintain ionic balance and/or to support other metabolic processes . Phosphocreatine stores are used to buffer ATP concentrations.

Postgrad Med, 1991 Jul, 90(1), 199 - 202, 205-8
Sepsis and septic shock . Deadly complications that are on the rise; Murray MJ et al.; Most patients are already hospitalized when sepsis and septic shock develop, and in spite of therapy, at least 50% die . Although newer therapeutic agents are being evaluated, current management consists of antibiotics, fluids for volume resuscitation, inotropic agents, and surgery for septic foci . Greater emphasis on preventive measures is recommended.

Crit Care Med, 1991 Jul, 19(7), 882 - 6
Postoperative sepsis: reexplore or observe? Accurate indication from diagnostic abdominal paracentesis; Halpern NA et al.; OBJECTIVE: To determine if postoperative diagnostic abdominal paracentesis is a useful clinical tool in the abdominal evaluation of the critically ill septic patient . DESIGN: Retrospective review . SETTING: Surgical ICU patients in a Veterans Administration medical center . PATIENTS: Ten patients were studied from a total of 1,053 patients admitted to the surgical ICU between September 1985 and May 1989 . INTERVENTIONS: Diagnostic abdominal paracentesis performed by the open or closed approaches . MEASUREMENTS AND MAIN RESULTS: Results are presented in three patient groups (A, B, and C): Group A (n = 4) had positive diagnostic abdominal paracentesis . Abdominal causes for the sepsis were found at reexploration . One of these four patients survived . Group B (n = 3) had negative diagnostic abdominal paracentesis . No abdominal septic source was found at reexploration; all three patients died . In group C (n = 3), diagnostic abdominal paracentesis was negative, patients were not reexplored, and all survived . Diagnostic accuracy correlated with three variables: a) the gross appearance and smell of the fluid, b) WBC count greater than 5000 or less than 500/mm3, and c) Gram stain demonstrating bacterial organisms . CONCLUSIONS: Diagnostic abdominal paracentesis proved accurate, reliable, simple, safe, and rapid in evaluating the abdomen in the postoperative septic patient . The use of this procedure should be considered in postoperative septic patients in whom an abdominal source for the sepsis needs to be excluded.

JPEN J Parenter Enteral Nutr, 1991 Jul-Aug, 15(4), 460 - 3
Tunneled central venous catheter sepsis: risk factors in a pediatric hospital; Mulloy RH et al.; All tunnelled central venous catheters (TCVC) placed at the Alberta Children's Hospital in Calgary, Alberta, between November 1984 and July 1987, were retrospectively reviewed to study the association of catheter infection with a number of factors including age, diagnosis, catheter use, and areas caring for children . One hundred children received 130 silastic catheters placed for a total of 17,861 days . Each catheter survived a median of 100 days . Thirty-one episodes of catheter sepsis were identified (one episode for each 576 days of catheter use) . Children under 2 years of age had more than two times the risk of catheter infection (p less than 0.01) . Children with malabsorption had a greater risk (45.7%) than did those with infection (25.0%) or cancer (15.5%) . The use of catheters for total parenteral nutrition (TPN) or for multiple purposes markedly increased the risk of catheter infection . The risk of infection of TCVC appears to be great in the young child, in particular, in those requiring TPN or multiple intravenous infusions . Use of TCVC in these children should be avoided if possible.

Circ Shock, 1991 Jul, 34(3), 311 - 8
Hyperdynamic sepsis in baboons: I . Aspects of hemodynamics; Schlag G et al.; The baboon has a number of advantages as a shock model, as its physiological as well as its biochemical behaviour is similar to man . Therefore we have tried to set up a model to mimic the early hyperdynamic phase of clinical sepsis . Seven baboons, 21-25 kg body weight were kept under EEG servocontrolled anesthesia for 8 hr . During this time live E . coli (ATC #33985) 2 x 10(10) BW/8 hr were continuously infused intravenously . Adequate fluid supply with Ringer's solution (up to 40 ml/kg/hr) was given to keep the pulmonary artery wedge pressure at baseline levels; this procedure resulted in a hyperdynamic response with a cardiac output (CO) 20-35% above baseline and a decrease (20-39%) in mean arterial pressure (MAP), leading to a 50% decrease in peripheral resistance . The pulmonary vascular changes were reflected in an increase of the mean pulmonary pressure (PA) to 42% above baseline and a marked rise in pulmonary vascular resistance (PVR) to 50% above baseline with no additional changes in pulmonary gas exchange . After 8 hr both CO and MAP were inversely correlated (r = 0.9-1) with dramatically increased catecholamine plasma levels (15 times above baseline) . With continuous infusion of live E . coli (blood levels 10(5)-10(6) CFU/ml) and massive fluid supply we have successfully mimicked hyperdynamic sepsis with severe organ failure after an 8-hr observation period.

Blood, 1991 Jun 15, 77(12), 2660 - 7
Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis; Kaufman N et al.; Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available . We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the alpha 2-macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab')2 derivative of a monospecific polyclonal antibody against alpha 2 M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody . The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4 degrees C in a range of 5 to 375 nmol/L . A close correlation of the ELISA with an amidolytic assay for alpha 2M-Kal was documented . Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of alpha 2M-Kal complex . Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks . Two other HAE patients did not show elevated levels at quiescent periods . The ELISA for alpha 2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks.

Aust N Z J Surg, 1991 Jun, 61(6), 469 - 71
Sepsis after Ivalon sponge rectopexy: an unusual case; Gupta S et al.; A case with an unusual presentation of sepsis after Ivalon sponge rectopexy is reported . A strong index of suspicion is important for correct diagnosis . Early removal of infected sponge allows quick resolution of the sepsis without recurrent prolapse.

Am J Physiol, 1991 Jun, 260(6 Pt 2), H1857 - 63
Chronic alcohol consumption enhances sepsis-induced cardiac dysfunction; McDonough KH et al.; Chronic alcoholism causes a cardiac contractile dysfunction which, in rats, may occur after 6 mo to 1 yr of alcohol consumption . Sepsis, on a more acute basis, can also induce intrinsic cardiac dysfunction . We tested the hypothesis that 2 mo of chronic alcohol feeding, while not directly causing overt depression of the myocardium, might sensitize the heart to a known cardiac stress, i.e., sepsis . We proposed that sepsis, induced in an alcoholic animal, would cause a more severe myocardial depression than in a nonalcoholic rat . Thus rats were fed a liquid diet with 36% of the total calories as alcohol for 8-10 wk and were then anesthetized and received an injection of live Escherichia coli (approximately 10(10) E . coli) through a dorsal subcutaneous catheter followed by a second dose approximately 5 h later . The following day, hearts were removed and, using the isolated working heart preparation, intrinsic contractile performance was assessed by generating ventricular function curves . Four groups of animals were studied . Hearts from the nonalcoholic-nonseptic group and the alcoholic-nonseptic group showed identical cardiac work (cardiac output x peak systolic pressure at the highest preload was 6,113 +/- 324 and 5,955 +/- 406 ml.min-1.mmHg-1, respectively) . Work in the nonalcoholic-septic and the alcoholic-septic groups was decreased by 30 and 50%, respectively (4,806 +/- 478 vs . 2,917 +/- 435 ml.min-1.mmHg-1 at the highest preload) . Thus 2 mo chronic alcohol consumption caused no overt cardiac dysfunction by itself but did exacerbate the myocardial injury induced by sepsis.

J Trauma, 1991 Jun, 31(6), 768 - 73; discussion 773-4
Dietary omega-3 fatty acids decrease mortality and Kupffer cell prostaglandin E2 production in a rat model of chronic sepsis; Barton RG et al.; We tested the hypothesis that substitution of omega-3 fat for dietary omega-6 fat would reduce mortality and decrease Kupffer cell prostaglandin E2 (PGE2) production in a rat model of chronic sepsis . Rats were fed via gastrostomy for 12 days with isonitrogenous, isocaloric diets containing 15% of calories as either safflower oil (omega-6) or a 10:1 mixture of menhaden oil (omega-3) and safflower oil . After five days of feeding, animals received an intra-abdominal abscess of defined bacterial content . Survivors were killed on post-laparotomy day 6 in conjunction with liver perfusion and protease liver digestion for Kupffer cell isolation . Kupffer cell PGE2 production was measured by radioimmunoassay after 18 hours of cell culture and again after stimulation with 0 LPS, 10 ng/ml LPS, and 10 micrograms/LPS . Mortality was decreased in menhaden oil-fed animals compared with safflower oil-fed animals (16% vs . 35%) . Kupffer cell PGE2 production was decreased in menhaden oil-fed animals at 18 hours (354 +/- 54 vs . 570 +/- 95 pg/0.1 ml; p = 0.09) and after stimulation with 10 micrograms/ml LPS (140 +/- 41 vs . 288 +/- 45 pg/0.1 ml; p = 0.03) compared with safflower oil-fed animals.

J Trauma, 1991 Jun, 31(6), 753 - 8; discussion 758-9
T3 preserves respiratory function in sepsis; Dulchavsky SA et al.; Sepsis produces profound hypothyroidism . This hypothyroid state is associated with altered lung metabolism and structural integrity . We studied the respiratory function of rats during sepsis-induced hypothyroidism with or without T3 treatment . Forty-four male Holtzman rats underwent cecal ligation and puncture (CLP) . Treatment was administered at six hours after surgery consisting of intraperitoneal injection of T3 (15 micrograms/kg, n = 19) or saline (n = 25) . At 20 hours (Group A) or 30 hours (Group B) following CLP, respiratory drive was assessed by serial occlusion pressure technique (P0.1) . The rats were killed and static elastance determined by serial air inflation to 10 cc . The lungs were excised for weight determination . The P0.1 values were significantly greater in T3-treated animals over controls in Group A (9.3 +/- 0.7 vs . 6.6 +/- 2.2, p less than 0.05 by t test); elastance was significantly improved by T3 treatment in Group B (p less than 0.05 by two-way ANOVA) . Lung weight, pH, pO2, pCO2, respiratory rate (RR), and mortality were not significantly different between groups . Control animals were hypothyroid by 20 hours after CLP (T3 less than 12.5 ng/dL) whereas T3-treated animals were euthyroid (T3 = 145 +/- 43 ng/dL) . Pulmonary dysfunction frequently accompanies sepsis; the euthyroid state appears protective . We found a significantly improved respiratory drive in septic animals with T3 treatment . Lung elastance was similarly improved in late sepsis with T3 treatment . The data suggest that T3 treatment preserves respiratory function in septic rats as evidenced by respiratory drive and compliance.

Crit Care Med, 1991 Jun, 19(6), 753 - 7
Amino acid alterations and encephalopathy in the sepsis syndrome; Sprung CL et al.; OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy . DESIGN: Retrospective analysis . SETTING: Medical wards and medical ICU of a university hospital . PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium . INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined . MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs . 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs . 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs . 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs . 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05) . Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality . APACHE II scores were higher in the septic shock patients (30 +/- 2 vs . 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs . 12%, p less than .01) . Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs . 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs . 61 +/- 7 mmol/L, p less than .05) than patients who survived . CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease.

AJR Am J Roentgenol, 1991 Jun, 156(6), 1163 - 6
Treatment of critically ill patients with sepsis of unknown cause: value of percutaneous cholecystostomy; Lee MJ et al.; Because of the difficulty in diagnosing acute cholecystitis in critically ill patients with severe intercurrent illness by clinical and imaging methods or percutaneous aspiration of the gallbladder, a trial of percutaneous cholecystostomy was performed in 24 patients in the intensive-care unit with persistent, unexplained sepsis after a complete clinical, laboratory, and radiologic search showed no alternative source of infection . Persistent high fevers, despite antibiotic therapy, were present in all patients, with elevated WBC count in 18 patients, vague abdominal tenderness in 11, and septic shock requiring vasopressors in 15 . Sonographically, all patients had distended, spherical gallbladders, six had gallstones, eight had wall thickening, three had pericholecystic fluid, and four had Murphy's sign . All patients were seen by a senior abdominal surgeon, who agreed to a trial of percutaneous cholecystostomy . Fourteen patients (58%) responded to percutaneous cholecystostomy, as evidenced by a decrease in WBC count, defervescence, and the ability to be weaned off vasopressors . Bile cultures were positive in four patients . Ten patients (42%) did not respond to percutaneous cholecystostomy; five eventually died of unrelated causes . A respiratory source of infection was eventually found in three of these 10 patients, with no proved source of infection in the remainder . No complications related to catheter insertion occurred in this group of patients . Bile leaks occurred in two patients when the percutaneous cholecystostomy catheter was removed, but without serious consequence . Our experience suggests that a lower threshold for performing percutaneous cholecystostomy in this difficult clinical subset of patients is worthwhile.

Circ Shock, 1991 Jun, 34(2), 252 - 62
Awake porcine model of intraperitoneal sepsis and altered oxygen utilization; Hoban LD et al.; We have characterized an awake swine model of septic shock . Hemodynamic, serum chemistry, and oxygen metabolism parameters were compared between eight septic and five sham animals . Eight male Yucatan miniature swine, weighing 20-28 kg, were anesthetized and catheters were placed in the pulmonary artery, external jugular, and the carotid artery . On day 2, 1.1-4.0 x 10(10) cfu Escherichia coli/kg were administered via an intraperitoneal catheter . Hemodynamic parameters were monitored hourly for 6 hours in awake animals . The animals were then placed back into the animal holding facility for clinical observation until the 24 hour post infusion measurements were taken . Septic animals were initially hypodynamic, with a decrease in cardiac index (CI) from a baseline value of 152.8 +/- 24.8 to 87.9 +/- 17.8 ml/kg/min (P less than .05) and an increased systemic vascular resistance index (SVRI) from a control value of 48.1 +/- 9.5 to 65.0 +/- 16.7 dynes*sec*cm-5/kg . At 24 hours post infusion, the animals were hyperdynamic with the CI increased to 211.0 +/- 27.2 ml/kg/min (P less than .05) and a decreased SVRI to 30.64 +/- 3.9 dynes*sec*cm-5/kg (P less than .05) . Oxygen utilization (VO2) increased during sepsis from 6.6 +/- 0.8 to 8.1 +/- 0.8 ml/kg/min at 6 hours (P less than .05) and remained elevated at 24 hours at 7.7 +/- 0.4 (P less than .05) . Increased oxygen consumption was attained with an increase in oxygen extraction (O2 ext) from 0.34 +/- 0.03 to 0.56 +/- 0.07 (P less than .05) during the first 6 hours of sepsis . At 24 hours, increased oxygen utilization was maintained by high oxygen delivery state . Significant alterations in serum chemistries in conjunction with post mortem evidence of multiple organ system failure were observed . Mortality on or before 4 days post infusion was 50% and positive blood cultures were obtained in 38% of the animals studied . This awake swine model serves as an excellent model to study metabolic pathophysiology and the treatment of septic shock.

Circ Shock, 1991 Jun, 34(2), 247 - 51
Amrinone during porcine intraperitoneal sepsis; Hermiller JB et al.; Seven Yucatan minipigs with chronic, severe intraperitoneal sepsis were given amrinone i.v . (loading dose of 0.75 mg/kg, followed by continuous infusion of 10, 20, 40, and 80 micrograms/kg/min) during the hyperdynamic phase of sepsis . Hemodynamic variables and oxygen utilization, delivery, and extraction were recorded throughout the study . Pulmonary capillary wedge pressure was kept constant to ensure a fixed ventricular filling pressure . Intravenous amrinone modestly augmented cardiac index without altering heart rate . Mean systemic and pulmonary arterial pressures decreased . Systemic and pulmonary vascular resistance fell significantly (P less than 0.05) . Amrinone did not significantly alter oxygen utilization or oxygen extraction, although oxygen delivery increased (P less than .05) . During the hyperdynamic phase of sepsis in this animal model, amrinone elicits vasodilatation with a modest improvement in stroke volume index . Consequently, cardiac output and oxygen delivery increased modestly . Because of its vasodilating properties and small salutary effects, amrinone is not an optimal first-line medication for hemodynamic stabilization during hyperdynamic sepsis.

Surg Clin North Am, 1991 Jun, 71(3), 549 - 65
Nutrition and metabolism in sepsis and multisystem organ failure; Baue AE; Sepsis and organ failure produce profound metabolic changes that contribute to hepatic and musculoskeletal failure . When multiple organ failure develops, the mortality rate is high, and therapy is unlikely to be effective unless the causative process (e.g., infection, low cardiac output) can be eliminated . Thus, the prevention of multiple organ failure and the prevention or early treatment of infection are paramount . Organ and nutritional support to prevent complications is necessary . The gastrointestinal tract should be used for nutrition whenever possible with a blenderized regular diet with fiber, glutamine, and short-chain fatty acids to protect and preserve the gut . If parenteral nutrition is necessary, special solutions may be necessary for the liver, kidneys, or lungs . If not, protein with 45% branched-chain amino acid, medium- and short-chain triglycerides, glutamine supplementation, and carbohydrates seem best . Other substances are being evaluated that may be helpful in nutrition and organ support, including arginine, xylitol, growth hormone, and anabolic steroids . Multiple organ failure should be prevented, if at all possible, by stopping or controlling the injury, removing as much necrotic tissue as possible, improving blood flow and oxygen consumption, supporting metabolism, and preventing infection or treating it early and adequately . Nutritional support plays a key role in preventing metabolic failure.

Clin Perinatol, 1991 Jun, 18(2), 361 - 81
Clinicopathologic approach to the diagnosis of neonatal sepsis; Gerdes JS; Perinatally acquired bacterial neonatal sepsis is a low-incidence, high-risk disease with a relatively benign treatment . Accurate diagnosis is difficult because there is no definitive diagnostic test; even blood cultures have an unacceptably low sensitivity . Therefore, the clinician must accept that a number of neonates will have treatment initiated for sepsis who do not have the disease . In order to treat rapidly all infants with sepsis and to minimize therapy for those without infection, historical, clinical, and laboratory data can be used together in a management approach to achieve optimal results.

Clin Otolaryngol, 1991 Jun, 16(3), 245 - 7
The management of peritonsillar sepsis by needle aspiration; Snow DG et al.; 172 consecutive patients admitted with suspected unilateral peritonsillar sepsis were studied . Needle aspiration of the peritonsillar space was performed, and they were all then treated with intravenous antibiotics (usually benzylpenicillin) . Any pus obtained was cultured . The aspiration was repeated if the patient was not improving after 24 h . A quantity of pus was aspirated at the first attempt from 91 patients (53%); 82 of these required no further aspiration but 7 required a further single aspiration and 2 required a further 2 aspirations before resolution of the sepsis . 71 of the 81 patients (88%) from whom pus had not been aspirated, and who were therefore initially considered to have peritonsillar cellulitis, required no further aspirations . However, 6 subsequently drained pus spontaneously and 4 produced a positive aspirate on a second occasion . Four patients required a change in their antibiotic therapy . We have found the combination of needle aspiration and parenteral antibiotics to be an effective treatment of peritonsillar sepsis . All patients were spared the unpleasant and painful experience of an incision and drainage procedure.

Anaesth Intensive Care, 1991 May, 19(2), 182 - 6
C-reactive protein as a diagnostic test of sepsis in the critically ill; Matson A et al.; Changes in the plasma concentration of C-reactive protein were assessed as a diagnostic test for sepsis in critically ill patients . Forty-nine episodes of secondary sepsis were identified in 31 patients . In 43 out of the 49 episodes there was a 25% or greater change in the concentration of C-reactive protein on the day that sepsis was diagnosed but in six episodes of sepsis the change was less than 25% . A 25% rise in the plasma concentration of C-reactive protein in the absence of other non-infective causes of a raised C-reactive protein, such as inflammation, tissue injury or surgery, is highly suggestive of infection, but failure of the C-reactive protein to rise does not eliminate a diagnosis of sepsis.

Ann R Coll Surg Engl, 1991 May, 73(3), 185 - 8
Early post-splenectomy sepsis after missile injury in adults; Ellias YA et al.; Early septic complications were studied in 292 patients operated on for penetrating missile injury of the abdomen with involvement of either the spleen or the liver, at Basrah Teaching Hospital between January 1983 and April 1986 . Depending on associated injuries, patients with splenectomy were divided into three groups, the first with isolated splenic injury, the second with splenic and associated extra-intestinal organ injury, and the third with splenic and intestinal injuries with or without extra-intestinal organ injury . Patients with hepatic injury were classified similarly . Splenectomy was carried out for any degree of splenic injury . Grade I hepatic injuries were managed by debridement and suturing while major grades II-IV underwent segmentectomy or lobectomy . Patients were considered septic if they had any three of four clinical criteria: temperature higher than 39 degrees C; significant haemodynamic deterioration; respiratory alkalosis, or oliguria . Of the total, 79 were excluded due to: early transfer 51, incomplete records 8, perioperative death 11, and having combined splenic and hepatic injuries 9 (excluded by definition), leaving 104 (74.8%) patients with splenectomy and 109 (71.1%) with hepatic injury available for study . Sepsis developed in 48 (46.1%) of patients after splenectomy and in 28 (25.7%) with hepatic injury . This difference was significant (P greater than 0.005) . In patients with isolated splenic injury, eight (25.8%) were septic while three (13.6%) of those with isolated hepatic injury developed sepsis . This was not significant (P = 0.32, Fisher's exact test) . When either was associated with an injury to an extra-intestinal organ, 15 (50%) of the splenectomy group developed sepsis compared to five (23.8%) of the hepatic injury group.(ABSTRACT TRUNCATED AT 250 WORDS)

J Surg Res, 1991 May, 50(5), 421 - 4
Human recombinant interleukin-1 alpha protection against the lethality of endotoxin and experimental sepsis in mice; Alexander HR et al.; Human recombinant interleukin-1 alpha (IL-1) has a diverse range of physiological activities which may be beneficial or deleterious to the host . Pretreatment with doses of IL-1 has been shown to protect mice against a subsequent lethal bacterial injection; however, the protective effects of a single intravenous (iv) dose of IL-1 have not been well characterized . The current experiments were performed to determine the best dose, timing, and duration of action of a single iv dose of IL-1 against a subsequent lethal challenge with intraperitoneal endotoxin (LPS) or experimental sepsis induced by cecal ligation and puncture (CLP) . Female C57B1/6 mice treated with iv IL-1 24 hr prior to 30 mg/kg LPS ip had improved survival compared to saline-treated controls (P less than 0.01) . IL-1 was also protective when given 6 to 72 hr, but not 2 or 96 hr, prior to LPS . IL-1 protection against LPS lethality was similar to protection seen with an iv dose of tumor necrosis factor (TNF) . After CLP, survival was improved with IL-1 versus saline pretreatment (P = 0.02) . Unlike previous work with TNF, no toxicity or lethality was observed at any dose of IL-1 administered . A single iv dose of IL-1 protects against the lethality of LPS and CLP in mice . IL-1 may be a useful treatment strategy in patients at risk for the development of life-threatening sepsis.

Am J Physiol, 1991 May, 260(5 Pt 1), E669 - 74
Increased pyruvate dehydrogenase kinase activity in response to sepsis; Vary TC; The effect of sterile inflammation and sepsis on the proportion of active pyruvate dehydrogenase complex (PDH) in mitochondria isolated from skeletal muscle has been investigated . The proportion of active PDH in mitochondria isolated from septic animals was significantly reduced compared with control under all incubation conditions examined, even in the presence of inhibitors of the PDH kinase . There was no significant difference between control and sterile inflammation in any of the incubations examined . The rate constant for ATP-dependent inactivation of the PDH complex in mitochondrial extracts from control animals was -0.42 min-1 (r = 0.993; P less than 0.001) and was not altered in mitochondrial extracts from sterile inflammatory animals (-0.43 min-1; r = 0.999; P less than 0.001) . However, rate constants for inactivation in septic animals was significantly increased over twofold to -1.08 min-1 (r = 0.987; P less than 0.001) (P less than 0.001 vs . control or sterile inflammation) . In the presence of inhibitors of the PDH kinase reaction (2.5 mM pyruvate or 1 mM dichloroacetate), inactivation of PDH after addition of ATP was significantly greater in mitochondrial extracts from septic than either control or sterile inflammatory animals . These results suggest that sepsis, but not sterile inflammation, induces a stable factor in skeletal muscle mitochondria that increased PDH kinase activity.

J Trauma, 1991 May, 31(5), 645 - 51; discussion 651-2
Down-regulation of homing receptors: a mechanism for impaired recruitment of human phagocytes in sepsis; Hasslen SR et al.; Receptors known as DREG adhesion molecules on human neutrophils and monocytes provide for homing of these phagocytic leukocytes to sites of inflammation . They mediate the initial adhesive interaction of the leukocytes to vascular endothelial cells and are then shed from the cell surface in response to chemotactic factors and inflammatory mediators . Systemic accumulation of these agents following major injury or sepsis may therefore promote shedding of DREG receptors from circulating leukocytes and impair their recruitment to sites of inflammation . To test this hypothesis, we have analyzed the expression of DREG receptors on neutrophils and monocytes from 25 patients admitted to the Surgical Intensive Care Unit . Receptor expression was measured by flow cytometry of cells stained with murine monoclonal DREG-56 anti-DREG antibody . For 14 nonseptic patients, mean monocyte positivity for DREG was reduced from 64% to 40% . For 11 septic patients, mean neutrophil and monocyte positivity for DREG was reduced from 94% to 82% and 64% to 34%, respectively . These results suggest that monocytes are more affected than neutrophils in vivo by conditions expected to stimulate shedding of DREG and that sepsis promotes shedding of these adherence receptors . Accumulation of DREG-negative monocytes in association with sepsis may be sufficient to impair their recruitment to inflammatory sites and limit their contribution to host defense against infection and tissue repair.

J Vasc Surg, 1991 May, 13(5), 677 - 82; discussion 682-4
Aortic sepsis: is there a role for in situ graft reconstruction?
Robinson JA, Johansen K.
Conventional extraanatomic reconstruction for aortic sepsis is associated with a significant risk of operative death, as well as frequent late complications . We evaluated in situ aortic grafting in the treatment of primary or graft-related aortic infection . Eleven selected patients underwent in situ aortic graft reconstruction in the setting of mycotic aneurysm (n = 5), secondarily infected aortic aneurysm (n = 1), primary aortoenteric fistula (n = 1), and secondary aortoenteric fistula (n = 4) . All patients survived: follow-up from 10 to 130 months reveals no evidence for graft thrombosis, pseudoaneurysm, new or recurrent aortoenteric fistula, or subsequent aortic operations in any patient . A literature review produced 110 cases of aortic sepsis managed by in situ aortic reconstruction during the last decade . Thirty-two patients (29%) either died in the operative period or suffered a lethal late complication associated with their aortic reconstruction . This mortality rate declined to 21% if patients undergoing incomplete removal of a contaminated graft were excluded, and to 19% with the addition of our 11 patients . Both our experience and that described in the literature suggest that, in properly-selected patients, in situ aortic graft replacement may be a rational treatment option for localized or circumscribed aortic sepsis.

Crit Care Med, 1991 May, 19(5), 732 - 5
Oxygen free radicals: effect on red cell deformability in sepsis; Powell RJ et al.; OBJECTIVE: To examine the effect of alpha-tocopherol, a free radical scavenger, on RBC deformability, mixed venous hemoglobin saturation (SvO2), arterial-venous oxygen content difference (C{a-v}O2), pHv, and survival during sepsis . DESIGN: Randomized controlled study . INTERVENTIONS: Sprague-Dawley rats were randomized to three groups: sham, cecal ligation and puncture, or alpha-tocopherol/cecal ligation and puncture (pretreatment with alpha-tocopherol before cecal ligation and puncture) . MEASUREMENTS AND MAIN RESULTS: The cecal ligation and puncture group had a significantly (p less than .05) higher SvO2 and lower C (a-v)O2, pHv, and survival rate when compared with alpha-tocopherol/cecal ligation and puncture and sham groups . No difference in pHa existed between groups . CONCLUSIONS: The alpha-tocopherol treatment improves survival in sepsis . RBC deformability during sepsis is prevented by alpha-tocopherol, suggesting that free radicals may cause the decrease in RBC deformability . This study provides indirect evidence that decreased RBC deformability may play a role in the physiologic peripheral shunting and decreased microcirculatory flow that occurs during sepsis.

Crit Care Med, 1991 May, 19(5), 705 - 11
Unaccounted for anion in metabolic acidosis during severe sepsis in humans; Mecher C et al.; OBJECTIVE: To quantitate the contribution of lactate, phosphate, urate, total serum proteins, and unidentified anions to the anion gap in patients with severe sepsis . DESIGN: Thirty critically ill patients with evidence of severe sepsis and systemic hypoperfusion were prospectively studied . MEASUREMENTS: The anion gap was calculated as {Na+} + {K+} - {Cl-} - {HCO3} . A corrected anion gap was calculated as the anion gap minus the anionic contribution of lactate, phosphate, urate, and total serum proteins . The corrected anion gap is a marker of unmeasured anion less unmeasured cation concentration . RESULTS: The mean anion gap was 21.8 +/- 1.4 mmol/L and the corrected anion gap was 3.7 +/- 0.8 mmol/L . The mean arterial blood lactate concentration was 5.9 +/- 0.8 mmol/L . The magnitude of the lactate concentration correlated linearly with the anion gap (r2 = .61, lactate = 0.4 anion gap - 3.9, n = 30, p less than .01) . The corrected anion gap was greater than 0 in 24 (80%) of 30 patients . The magnitude of the corrected anion gap correlated linearly with the anion gap (r2 = .66, corrected anion gap = 0.5 anion gap - 6.3, n = 30, p less than .01) . Since the slope of the regression line for estimating corrected anion gap from anion gap was 0.5, the contribution of unmeasured anions was as important as lactate in determining the anion gap . CONCLUSION: These data indicate that lactic acidosis does not entirely account for the metabolic acidosis during severe sepsis . Furthermore, the increased corrected anion gap suggests the presence of an unidentified anion (or anions) that is (or are) responsible, in large part, for the development of metabolic acidosis in patients with sepsis.

Crit Care Med, 1991 May, 19(5), 664 - 71
Oxygen consumption in sepsis and septic shock; Tuchschmidt J et al.; This review article examines the pathophysiology of septic shock, with special attention to the concept of supply-dependent consumption and the implications this concept has for therapy . Patients with septic shock require higher levels of oxygen delivery (DO2) to maintain aerobic metabolism . When DO2 is inadequate, peripheral tissues switch to anaerobic metabolism and oxygen consumption decreases . The lactic acidosis that occurs is a reasonable clinical marker of supply dependency and inadequate tissue perfusion . Maximizing DO2 is an important part of the hemodynamic resuscitation of patients with septic shock . To achieve this goal, intravascular volume must be restored and the myocardial depression associated with sepsis must be treated to optimize cardiac output . The normalization of arterial lactate concentration is a reasonable goal of resuscitative efforts.

Crit Care Med, 1991 May, 19(5), 613 - 8
Physiologic stress and cellular ischemia: relationship to immunosuppression and susceptibility to sepsis; Abraham E; Multiple organ system failure secondary to infection is the most frequent cause of late mortality after hemorrhage, burns, and trauma . Although multiple immunologic abnormalities have been identified following injury, blood loss, and tissue ischemia, the mechanisms that produce these alterations in T- and B-cell function have not been completely defined . Physiologic stress and ischemia result in increased release of neuroendocrine peptides and hormones, capable of affecting normal neuroendocrine-immunologic balance and producing immunosuppression . Tissue ischemia leads to increased expression of heat shock proteins by hypoperfused cells, which can alter T-cell function . Injury also is followed by the appearance of serum immunosuppressive factors, which have been shown to inhibit T- and B-cell function . Future therapies directed at these and other cellular and molecular abnormalities initiated by tissue hypoperfusion may reverse the immunosuppressed state in critically ill patients and lead to improved outcome in this setting.

Ann Surg, 1991 May, 213(5), 401 - 9; discussion 409-10
Brush border transport of glutamine and other substrates during sepsis and endotoxemia; Salloum RM et al.; The effects of severe infection on luminal transport of amino acids and glucose by the small intestine were investigated . Studies were done in endotoxin-treated rats and in septic patients who underwent resection of otherwise normal small bowel . In rats the kinetics of the brush border glutamine transporter and the glutaminase enzyme were examined . In patients the effects of severe infection on the transport of glutamine, alanine, leucine, and glucose were studied . Transport was measured using small intestinal brush border membrane vesicles that were prepared by Mg++ aggregation/differential centrifugation . Uptake of radiolabeled substrate was measured using a rapid mixing/filtration technique . Vesicles demonstrated 15-fold enrichments of enzyme markers, classic overshoots, transport into an osmotically active space, and similar 2-hour equilibrium values . The sodium-dependent pathway accounted for nearly 90% of total carrier-mediated transport . Kinetic studies on rat jejunal glutaminase indicated a decrease in activity as early as 2 hours after endotoxin secondary to a decrease in enzyme affinity for glutamine (Km = 2.23 +/- 0.20 mmol/L {millimolar} in controls versus 4.55 +/- 0.67 in endotoxin, p less than 0.03), rather than a change in Vmax . By 12 hours the decrease in glutaminase activity was due to a decrease in Vmax (222 +/- 36 nmol/mg protein/min in controls versus 96 +/- 16 in endotoxin, p less than 0.03) rather than a significant change in Km . Transport data indicated a decrease in sodium-dependent jejunal glutamine uptake 12 hours after endotoxin secondary to a 35% reduction in maximal transport velocity (Vmax = 325 +/- 12 pmol/mg protein/10 sec in controls versus 214 +/- 8 in endotoxin, p less than 0.0001) with no change in Km (carrier affinity) . Sodium-dependent glutamine transport was also decreased in septic patients, both in the jejunum (Vmax for control jejunum = 786 +/- 96 pmol/mg protein/10 sec versus 417 +/- 43 for septic jejunum, p less than 0.01) and in the ileum (Vmax of control ileum = 1126 +/- 66 pmol/mg protein/10 sec versus 415 +/- 24 in septic ileum, p less than 0.001) The rate of jejunal transport of alanine, leucine, and glucose was also decreased in septic patients by 30% to 50% (p less than 0.01) . These data suggest that there is a generalized down-regulation of sodium-dependent carrier-mediated substrate transport across the brush border during severe infection, which probably occurs secondary to a decrease in transporter synthesis or an increase in the rate of carrier degradation.(ABSTRACT TRUNCATED AT 400 WORDS)

Am Rev Respir Dis, 1991 May, 143(5 Pt 1), 1083 - 7
Differential activation of mixed venous and arterial neutrophils in patients with sepsis syndrome and acute lung injury; Nahum A et al.; Neutrophil (PMN) functions, such as production of toxic oxygen (O2) metabolites, adherence, and chemotactic properties, are modified during local tissue inflammation and sepsis . We hypothesized that PMN would be primed during their transit through injured tissue beds, which in turn can lead to modulation or retention of the primed PMN by downstream tissues like the lungs . We tested this hypothesis by measuring the transpulmonary gradient of hydrogen peroxide (H2O2) production by zymosan-activated PMN . We examined the mixed venous to arterial difference in H2O2(delta H2O2) produced by zymosan-activated PMN in septic patients without lung infiltrates, patients with lung injury, and a control group of patients undergoing elective surgery or coronary catheterization . Septic patients had higher mixed venous H2O2/10(6) PMN, whereas lung injury patients had higher arterial H2O2/10(6) PMN . The control group had the same H2O2/10(6) PMN in mixed venous and arterial blood . The delta H2O2 in septic, lung injury, and control groups were 0.35 +/- 0.22, -0.31 +/- 0.48, and -0.01 +/- 0.04 nmol H2O2/10(6) PMN, respectively . The mixed venous to arterial H2O2 gradient distinguished septic patients from the control and lung injury patients (p less than 0.05) . Our results are consistent with the hypothesis that in septic patients PMN are primed in the periphery and downregulated or sequestered in the lung, and in lung injury patients PMN are primed in the lung and sequestered in the periphery . Alternatively, neutrophil-endothelial interactions may downregulate toxic O2 metabolite production by PMN during their transit through microvascular beds.

Chest, 1991 May, 99(5), 1072 - 5
Peripheral vascular tone in sepsis; Astiz ME et al.; Septic shock is characterized as a distributive form of circulatory failure . We examined the relationship of changes in forearm arterial, venous, and microvascular tone to the severity of sepsis . The study population consisted of ten control patients, 15 patients with sepsis, and eight patients with sepsis and shock . Patients treated with inotropic, vasopressor, or vasodilator drugs were excluded from the study . Forearm venous capacity (MVC), forearm venous tone (F-VT), arterial blood flow (FBF), forearm arterial resistance (FAR), and hyperemic response (FBF-RH) were measured using air plethysmography . MVC was decreased and VT increased in septic and septic shock patients . FBF was decreased with modest increases in FAR in septic and septic shock patients . FBF-RH was significantly reduced in both septic and septic shock patients . Decreases in FVT and attenuation of the reactive response to hyperemia occurred early in sepsis in patients without clinical evidence of hypoperfusion . In our patients, progressive vasodilatation in skeletal muscle was not associated with severe sepsis . These changes appear to be proportional to the severity of sepsis and are most pronounced in patients with circulatory failure.

Vestn Rentgenol Radiol, 1991 May-Jun, (3), 11 - 7
{The clinico-radiographic picture of pulmonary-pleural complications in sepsis}; Mustafin DG; Proceeding from the investigation and therapy of 106 patients with pleuropulmonary complications of sepsis the authors described clinical and x-ray features of different types of their course, complications and outcomes . In 58% of cases pulmonary lesions were detected at the stage of pyodestruction and pleural empyema; interstitial-focal and infiltrative pneumonias of considerable spreading with the development of a respiratory type of septic shock were observed less frequently . Pulmonary lesions in 24% were the only sign of septicopyemia, in 58% they prevailed in the clinical picture of polyorganic lesions; pleural complications developed in 32% of the patients . Convalescence was observed in 88 (83%) patients; they had residual bullous-sclerotic pulmonary changes . The lethality rate was 17%.

Anesteziol Reanimatol, 1991 May-Jun, (3), 53 - 5
{Optimization of the functional activity of the adrenal cortex in patients with sepsis}; Spas VV et al.; The effect of hemosorption on adrenal steroidogenic reactions has been studied in 75 patients with sepsis . Different variants of steroidogenesis optimization have been used . Hemosorption led to an increase in the level of steroid hormones, with this background retained throughout the whole treatment period . The most effective of all the variants of stress adrenal steroidogenic reactions optimization was the application of B, B1, B6, B12 vitamin complex and taktivin . The least effective was the application of B vitamin complex, taktivin and ultraviolet blood irradiation . The technique elaborated makes it possible to avoid an increase in steroid blood level during treatment, which must have a favorable effect on the recovery of immune homeostasis in the patients.

Infection, 1991 May-Jun, 19(3), 146 - 9
Neonatal sepsis in an intensive care unit and results of treatment; Simon C et al.; Incidence and fatality of neonatal sepsis in intensive care units have been relatively high despite progress in the management of very ill neonates and combined treatment of sepsis with antibiotics . Between 1985 and 1989 944 children (632 premature babies and 312 term babies) were treated in the intensive care unit of the University Children's Hospital of Kiel . The incidence of sepsis was 5% (congenital sepsis 4%, sepsis acquired after birth 1%) . Pneumonia occurred in 4% (congenital pneumonia in 2%, postnatal pneumonia in 2%) . Early diagnosis and treatment with piperacillin plus cefotaxime reduced the mortality rate of sepsis to 2% . Sepsis never developed under treatment with piperacillin plus cefotaxime . Early recognition of neonatal sepsis by a good blood culture technique and beginning of treatment on first suspicion of sepsis with cefotaxime and piperacillin can improve the results especially in intensive care patients.

Surg Gynecol Obstet, 1991 May, 172(5), 415 - 24
The role of platelet activating factor and its antagonists in shock, sepsis and multiple organ failure; Anderson BO et al.; PAF has been implicated as a mediator of shock, sepsis and MOF . The results of experimental data demonstrate that PAF induces changes characteristic of endotoxemia and sepsis, including systemic hypotension and diffuse microvascular leakage . These effects are prevented by PAF antagonists . PAF induces many of the characteristic changes of MOF, including functional impairment in the lung, kidney, gastrointestinal tract and heart . PAF antagonists will inhibit these adverse effects . PAF antagonists are now being manufactured by a number of pharmaceutical companies studying the beneficial effects of PAF antagonists in human disease . Data from these studies promise valuable information with significant clinical relevance to the practicing surgeon.

Vnitr Lek, 1991 May, 37(5), 514 - 7
{Disseminated intravascular coagulation and sepsis}; Sevcik P et al.; The authors give an account on the relations between disseminated intravascular coagulation, sepsis and multiorgan failure . Disseminated intravascular coagulation is defined as an acquired disorder of blood clotting with an increased turnover of thrombocytes, fibrinogen and coagulation factors . The authors discuss aetiopathogenetic aspects, possibilities of laboratory diagnosis, anticoagulation and substitution therapy and prophylaxis of disseminated intravascular coagulation in septicaemia . They emphasize comprehensive treatment of septicaemias where haematological monitoring and therapy must form an integral part . In an extensive series of septic multiorgan failures the authors detected failures apparent on laboratory examination in 41% of the patients.

Srp Arh Celok Lek, 1991 May-Jun, 119(5-6), 143 - 4
{Thrombophlebitis of the sigmoid sinus and otogenic sepsis}; Dergenc R et al.; Lateral sinus trombophlebitis and sepsis otogenes are rare complications of chronic osteitic otitis, but often resulting in delayed recognition and high mortality rate . During ten years in the period 1979-1989, we cured 5 patients with lateral sinus pathology and sepsis otogenes . All patients were successfully cured by surgical and conservative treatment . The incidence of these complications in our results confirm the events in recent literature that it is rare but complex condition with widespread clinical features which may range from subtle signs to gross toxaemia.

Eur Cytokine Netw, 1991 May-Jun, 2(3), 177 - 82
Interleukin-6 (IL-6) and acute-phase proteins in rats with biliary sepsis; Scotte M et al.; We measured serum interleukin-6 (IL-6) and acute-phase proteins, alpha 1-acid glycoprotein (AGP) and alpha 2-macroglobulin (alpha 2M), after a retrograde intrabiliary bacterial infection in rats with biliary obstruction . Maximum serum IL-6 was obtained at 6 h in rats following inoculation of bacteria (10(6) CFU/ml E . Coli) in the bile duct and it was higher than that observed in rats undergoing a bile duct ligation or a laparotomy . There was a strict relationship between the level of IL-6 at 6 h and the modified levels of AGP and alpha 2M at 48 h . AGP and alpha 2M levels were the highest in sera of rats with bile duct infection as compared with those found in sera of rats with bile duct ligation or laparotomy . After inoculation of E . Coli or E . Fecalis, blood IL-6 level was always higher at 6 h in inferior vena cava as compared with that found in the supra hepatic vein . These results indicate that IL-6 is synthesized after a biliary sepsis and that its blood level is higher in the systemic circulation than in the local circulation.

Vestn Rentgenol Radiol, 1991 May-Jun, (3), 11 - 7
{Clinical and radiologic manifestations of pleural and pulmonary complications in sepsis}; Mustafin DG; Proceeding from the investigation and therapy of 106 patients with pleuropulmonary complications of sepsis the authors described clinical and x-ray features of different types of their course, complications and outcomes . In 58% of cases pulmonary lesions were detected at the stage of pyodestruction and pleural empyema; interstitial-focal and infiltrative pneumonias of considerable spreading with the development of a respiratory type of septic shock were observed less frequently . Pulmonary lesions in 24% were the only sign of septicopyemia, in 58% they prevailed in the clinical picture of polyorganic lesions; pleural complications developed in 32% of the patients . Convalescence was observed in 88 (83%) patients; they had residual bullous-sclerotic pulmonary changes . The lethality rate was 17%.

Nutr Clin Pract, 1991 Apr, 6(2), 43 - 8
Culture methods to evaluate central venous catheter sepsis; Curtas S et al.; Sepsis is a frequent complication of central venous catheters, but the diagnosis of catheter sepsis is not always clear-cut . A variety of culture methods is available to determine catheter-related septicemia . Each method has advantages and disadvantages for the clinician to consider . This article reviews qualitative, quantitative, and other culture methods applicable to both blood and the device.

Circ Shock, 1991 Apr, 33(4), 222 - 7
Elevated plasma levels of endothelin in patients with sepsis syndrome; Weitzberg E et al.; The levels of the recently isolated endothelial-derived peptide, endothelin, which has potent vasoconstrictor properties, were analyzed by radioimmunoassay in plasma from six patients with sepsis syndrome . For comparison endothelin levels were also measured in plasma from ten healthy volunteers . In the septic group plasma endothelin-like immunoreactivity was five-fold higher (11.3 +/- 2.8 pmol/l) compared to the volunteers (2.4 +/- 0.07 pmol/l) (P less than 0.01) . Three patients had anuria and were found to have the highest plasma endothelin levels, maximally 23.8 pmol/l . In the septic group plasma endogenous norepinephrine was increased to 8.3 +/- 2.2 nmol/l, as compared to 0.98 +/- 0.09 nmol/l in healthy volunteers (P less than 0.01) . The results confirm that the sympathetic nervous system is activated in the septic patient . Plasma levels of endothelin, probably emanating from damaged endothelial cells by bacterial toxins, are also elevated indicating that this peptide may be involved in vasoconstrictor responses resulting in organ failure, which so often is encountered in septicemia.

Circ Shock, 1991 Apr, 33(4), 200 - 6
Sepsis in the young rat: maternal milk protects during cecal ligation and puncture sepsis but not during endotoxemia; Witek-Janusek L et al.; Cecal ligation and puncture (CLP) sepsis and the impact of maternal milk were studied in young rats from 10 to 28 days of age . Ten- and 14-day-old rats were highly resistant to CLP; 24 hr survival was 90% and 97%, respectively . However, survival decreased to 55% and 30%, respectively, in 21- and 28-day-old rats . No differences in plasma glucose and lactate were seen in rats from 10 to 18 days of age, but 21-day-old rats became significantly hypoglycemic and hyperlacticacidemic after CLP . In rats maintained on an exclusive maternal milk diet from 14 to 21 days of age, survival after CLP was improved (55% versus 94%); P less than .05), hypoglycemia did not occur, and hyperlacticacidemia was blunted . But this protective effect of maternal milk was not observed during endotoxemia in the young rat . These results suggest important differences between the models of CLP sepsis and endotoxemia in the young rat.

J Pediatr Surg, 1991 Apr, 26(4), 483 - 5; discussion 485-6
The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model; Jackson RJ et al.; In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier . The newborn rabbit provides an excellent model to study these factors . Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding . This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli . New Zealand white rabbit pups (2 to 5 days old) were studied . The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated . Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation . No bacteria were isolated from the colons of all but one control animal . Translocation or systemic sepsis did not occur . Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%) . Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%) . Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis . This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.

Arch Dis Child, 1991 Apr, 66(4), 488 - 90
Breast feeding and protection against neonatal sepsis in a high risk population; Ashraf RN et al.; Protection against neonatal sepsis by breast feeding was investigated in a developing community . A case-control study was carried out with 42 cases from a hospital and 270 controls, matched for age and socioeconomic conditions from the community . Exclusive breast feeding was extremely rare, most babies being partially breast fed and a few being given formula feed or animal milk . A highly significant odds ratio of 18 was obtained, showing that even partial breast feeding protects against neonatal sepsis in such a population.

Crit Care Med, 1991 Apr, 19(4), 512 - 7
Blood transfusion and oxygen consumption in surgical sepsis; Steffes CP et al.; OBJECTIVE: To evaluate the use of serum lactic acid values to predict flow-dependent increases in oxygen consumption (VO2) in response to increasing oxygen delivery (DO2) after blood transfusion in surgical sepsis . DESIGN: Prospective study . SETTING: Tertiary care, trauma center . PATIENTS: Twenty-one patients, postsurgical or posttrauma, judged septic by defined criteria . INTERVENTIONS: Serum lactic acid concentrations, DO2, and VO2 were measured before and after transfusion therapy . MEASUREMENTS AND MAIN RESULTS: Overall, the DO2 increased from 532 +/- 146 to 634 +/- 225 (SD) mL/min.m2 (p less than .001), and the VO2 increased from 145 +/- 39 to 160 +/- 56 mL/min.m2 (p = .02) . These changes occurred with an Hgb increase from 9.3 +/- 1.1 to 10.7 +/- 1.5 g/dL (p less than .001) . The patients were grouped by their pretransfusion serum lactic acid values . In those patients with normal (less than 1.6 mmol/dL) serum lactic acid (n = 10), DO2 increased from 560 +/- 113 to 676 +/- 178 mL/min.m2 (p less than .02), and VO2 increased from 150 +/- 25 to 183 +/- 46 mL/min.m2 (p less than .02) . However, in the increased serum lactic acid group (n = 17), VO2 was not significantly changed after transfusion (143 +/- 46 to 146 +/- 58 mL/min.m2) despite increased DO2 (515 +/- 163 to 609 +/- 251 mL/min.m2, p less than .01) . CONCLUSIONS: Blood transfusion can be used to augment DO2 and VO2 in septic surgical patients . Increased serum lactic acid values do not predict patients who will respond . The absence of lactic acidosis should not be used in this patient population to justify withholding blood transfusions to improve flow-dependent VO2 . Patients who have increased lactate concentrations may have a peripheral oxygen utilization defect that prevents improvement in VO2 with increasing DO2.

Surgery, 1991 Apr, 109(4), 497 - 501
Transient inhibition of neutrophil adherence with the anti-CD18 monoclonal antibody 60.3 does not increase mortality rates in abdominal sepsis; Mileski WJ et al.; Monoclonal antibodies (MAbs) that recognize the neutrophil (PMN) adherence complex CD11/CD18 inhibit PMN adherence to endothelium and attenuate PMN-mediated ischemia-reperfusion injury . One consideration regarding the clinical usefulness of such therapy is whether transient inhibition of PMN adherence or function will impede host defense and increase susceptibility to infection and sepsis . We studied susceptibility to sepsis in New Zealand white rabbits with an appendiceal devascularization model to answer the question: Does inhibition of PMN adherence with the anti-CD18 MAb 60.3 increase morbidity and mortality rates in abdominal sepsis? Four treatment groups of 10 animals each were studied: group 1 (controls) received no treatment, group 2 received MAb 60.3, group 3 was given the antibiotic cefazolin alone, and group 4 received both cefazolin and MAb 60.3 . PMN emigration into the peritoneum was inhibited significantly in MAb 60.3-treated animals (groups 2 and 4) . There was no difference in weight loss, incidence of infectious complications, or mortality rates when MAb 60.3-treated animals were compared with untreated animals . These results demonstrate that transient inhibition of PMN adherence does not increase morbidity or mortality rates in this model of abdominal sepsis . These results suggest that if MAb 60.3 or similar antibodies are used to prevent PMN-mediated injury, they will not increase susceptibility to sepsis.

Surgery, 1991 Apr, 109(4), 468 - 73
Effect of the glucocorticoid receptor antagonist RU 38486 on muscle protein breakdown in sepsis; Hall-Angeras M et al.; The role of glucocorticoids in muscle catabolism during sepsis was tested with the glucocorticoid receptor antagonist RU 38486 . Sepsis was induced in male Sprague-Dawley rats (40 to 60 gm) by cecal ligation and puncture (CLP) . Other animals underwent sham operation . Two hours before CLP or sham operation, rats received RU 38486 (5 mg/kg) or a corresponding volume of vehicle by gavage . Sixteen hours after CLP or sham operation, protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus muscles . Total and myofibrillar protein breakdown rates were determined by measuring net release of tyrosine and 3-methylhistidine, respectively . The protein synthesis rate was approximately 30% lower in rats with sepsis than in sham operated rats and was not affected by treatment with RU 38486 . The total protein breakdown rate was increased by approximately 70% and myofibrillar protein degradation was increased more than fivefold in muscle from rats with sepsis . Treatment with RU 38486 resulted in a 28% reduction of total and a 44% reduction of myofibrillar protein breakdown in rats with sepsis but did not affect proteolysis in muscle from sham-operated animals . The results support a role of glucocorticoids in accelerated muscle proteolysis during sepsis . It is not clear whether glucocorticoids are the only required mediator or they interact with other substances to induce muscle protein breakdown during sepsis.

J Clin Endocrinol Metab, 1991 Apr, 72(4), 945 - 53
Elevated serum diiodotyrosine (DIT) in severe infections and sepsis: DIT, a possible new marker of leukocyte activity; Meinhold H et al.; Ether link cleavage (ELC) of T4 yielding diiodotyrosine (DIT) has recently been shown in vitro to be the major pathway of T4 metabolism in phagocytosing leukocytes . To evaluate this pathway in vivo and the possible clinical relevance of DIT measurements in diseases with increased leukocyte activity, radioimmunological studies on serum levels of DIT and other thyroid parameters were performed in 125 critically ill patients classified into 3 groups with bacterial infections according to the severity of infection and 1 group without infections . While the pattern of iodothyronine and TSH levels typical for severe nonthyroidal disorders, i.e . decreased total T3 and elevated rT3, normal or decreased total T4 and TSH, and normal free T4, was found in all four groups of intensive care patients studied, elevated serum DIT was observed only in those patients whose clinical course was complicated by severe bacterial infections . Serial measurements revealed a close temporal connection between the infection phase and increased DIT levels . Median values and 16th to 84th percentile ranges (in parentheses) of serum DIT (normal range, 0.02-0.55 nmol/L) were as follows: sepsis, 1.38 (0.32-5.14); severe nonsystemic infections such as peritonitis and abscesses, 3.84 (0.24-17.2); moderate infections such as pneumonia and tracheobronchitis, 0.44 (0.18-1.16); and critical illness without infections, 0.14 (0.08-0.30) nmol/L . These elevations of circulating DIT could neither be correlated with changes in renal function nor attributed to drug effects . The results of the present study do not allow any definitive conclusions to be made about the mechanisms underlying the phenomenon of increased serum DIT levels in infections . Apart from this open question, DIT appears to be a relatively specific serum parameter for the presence and course of severe bacterial inflammations . Its measurement could provide useful clinical information, particularly for monitoring the time course of deep-seated infections.

J Natl Med Assoc, 1991 Apr, 83(4), 325 - 8
L-alpha-phosphatidylcholine-induced stimulation of PGI2 production in canine gallbladders following hypovolemic shock and Escherichia coli sepsis; Hoover EL et al.; In vitro production of PGI2 in canine gallbladders subjected to hypovolemic shock and Escherichia coli sepsis was studied to determine whether a precursor above arachidonic acid in the cyclooxyenase cascade might be operative in the production of prostacyclin, which, in turn, may play a role in the pathogenesis of acute acalculous cholecystitis (AC) . L-alpha-phosphatidylcholine (LaP), an arachidonic acid precursor, was used as the test agent . LaP did not stimulate PGI2 production from either gallbladder surface in the hypovelimic animals or the mucosa of the septic shock group . However, it did stimulate PGI2 production from the SS serosa compared with controls, 1375 +/- 432 versus 633 +/- 198 pg/cm2/min (P less than .05) . In conclusion, lack of stimulation of PGI2 in the hypovolemic model suggests that PGI2 does not play a role in AC . Alternatively, it may play a role in preventing this disease process in septic shock . This study demonstrates the use of precursors of arachidonic acid and the cyclooxygenase pathway as active participants in the production of PGI2, although it is unclear whether the prostacyclin produced helps prevent AC in septic shock.

Crit Care Clin, 1991 Apr, 7(2), 437 - 50
Infections and sepsis in disasters; Steinberg SM et al.; It seems reasonable to expect that infections will occur after certain types of disasters . There are some data to support this conjecture in studies of tornadoes, hurricanes, and mass trauma situations . We have tried to extrapolate from these data what we believe will be the infectious effects of different types of disasters, taking into account the potential for alteration in the host secondary to injury, the modification of living conditions, and the possibility of the disruption of medical care.

Mikrobiyol Bul, 1991 Apr, 25(2), 151 - 9
{The value of laboratory tests for the early diagnosis of newborn sepsis}; Hancioglu E et al.; In our study, laboratory tests were evaluated in the early diagnosis of newborn sepsis . The study consisted of 53 newborn infants with the diagnosis of suspected sepsis . Of the 53 newborn infants twenty seven were excluded from the study, because of negative blood culture . Remaining 26 newborns with positive blood culture and 15 healthy newborns comprised the study (sepsis group) and control group respectively . Total mature neutrophil count, immature/total neutrophil and immature/matur neutrophil ratio, toxic granulation changes, serum level of C-reactive protein and haptoglobin were found statistically higher in sepsis group than control group . Thrombocyte count and serum level of IgG were significantly lower in sepsis group . Average total white blood cell count, result of nitroblue tetrazolium tests erythrocyte sedimentation rate and serum level of IgM was similar in both groups . We emphasized that hematological scoring system, serum level of C-reactive protein and haptoglobins can be used in the early diagnosis of newborn sepsis.

Thromb Haemost, 1991 Mar 4, 65(3), 291 - 5
Fibrinolysis and coagulation in patients with infectious disease and sepsis; Philippe J et al.; Sepsis is often associated with hemostatic dysfunction . This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome . Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease . The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p less than 0.0001) . PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01) . AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001) . No significant difference was found for t-PA antigen nor for PAI activity . Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity . It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection . u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

Am J Perinatol, 1991 Mar, 8(2), 91 - 3
Can the nonstress test predict congenital sepsis?
Gonen R, Ohlsson A, Farine D, Milligan JE.
The possible role of the nonstress test (NST) in the prediction of congenital sepsis in pregnancies complicated by prolonged premature rupture of the membranes (PROM) was investigated in a retrospective controlled study . Thirteen NSTs performed within 24 hours of the delivery of infants with congenital sepsis were coded, blinded, and mixed with an equal number of blinded NSTs derived from randomly selected patients matched for gestational age with PROM but without neonatal or maternal infection . Eleven of 13 infants with congenital sepsis had a reactive NST, and two had a nonreactive test . Among the controls, there were also 11 reactive and two nonreactive NSTs . The sensitivity and specificity of the NST in predicting congenital sepsis in patients with PROM were 15.4% and 84.6%, respectively . The positive predictive value and the negative predictive value were 50% . Our results suggest that the NST is not a useful tool for prediction of congenital sepsis.

Am J Physiol, 1991 Mar, 260(3 Pt 1), E453 - 8
Interrelationship between hepatic ureagenesis and gluconeogenesis in early sepsis; Ohtake Y et al.; This study was performed to investigate the interrelationship between gluconeogenesis and ureagenesis during sepsis . In isolated perfused livers, gluconeogenesis was assessed using either lactate or a combination of lactate, glutamine, and alanine as substrate . Ureagenesis was assessed using either NH4Cl or glutamine plus alanine as substrate . NH4Cl stimulated urea production in livers from both septic and sham-operated control rats . Urea release was approximately 1.2 and 2.0 mg urea nitrogen.g-1.h-1 for 1 and 5 mM NH4Cl, respectively, and was equal for both groups . With amino acids as substrate, urea production was significantly greater in livers from septic animals compared with controls . Phenylephrine stimulated urea production in the sham-operated group by about twofold, whereas in the septic group urea release was slightly inhibited . Gluconeogenesis from lactate was inhibited by NH4Cl (1 and 5 mM) in both groups, with no difference between groups . In contrast to enhanced ureagenesis from amino acids in septic rats, gluconeogenesis was decreased by approximately 24% (P less than 0.5) . Similarly, phenylephrine (1 microM) stimulated gluconeogenesis by 13 +/- 1 mumol.g-1.h-1 in sham-operated rats but only by 9 +/- 1 mumol.g-1.h-1 in septic rats (P less than 0.02) . These results suggest that hepatic gluconeogenic and ureagenic pathways are intact in sepsis but that altered substrate preference and hormone sensitivity may result in decreased gluconeogenesis in the presence of elevated amino acid levels.

Metabolism, 1991 Mar, 40(3), 247 - 51
Influence of sepsis in rats on muscle protein turnover in vivo and in tissue incubated under different in vitro conditions; Hall-Angeras M et al.; We studied the influence of sepsis on muscle protein synthesis and degradation in vivo and in muscles, incubated flaccid or at resting length . Sepsis was induced in rats by cecal ligation and puncture (CLP) . Control rats were sham-operated . A flooding dose of 14C-phenylalanine was used to determine muscle protein synthesis rate in vivo, and protein breakdown was calculated from the difference between protein synthesis and growth rates . Protein synthesis rate in vitro was assessed by determining incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles . Total and myofibrillar protein breakdown rates were determined from release into incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively . Muscle protein synthesis rate in vivo was reduced by 35%, similar to the reduction observed in muscles incubated flaccid or at resting length . The calculated protein breakdown rate in vivo was increased by 31% in septic rats . In incubated muscles, the increase in total protein breakdown (ie, tyrosine release) during sepsis was almost identical in muscles incubated flaccid or at resting length, ie, 83% to 88% in EDL and 47% to 49% in SOL . Myofibrillar protein degradation in vitro (ie, 3-MH release) was increased approximately 10-fold in EDL muscles incubated flaccid or at resting length, but was not significantly affected by sepsis in SOL . Results suggest that sepsis-induced changes in protein synthesis observed in muscles incubated either flaccid or at resting length reflect changes in vivo . Changes in protein breakdown were qualitatively similar in vivo and in vitro, but results in incubated muscles may overestimate the increase in muscle proteolysis caused by sepsis.

Ann Surg, 1991 Mar, 213(3), 261 - 4
Elevated plasma endothelin-1 concentrations are associated with the severity of illness in patients with sepsis; Pittet JF et al.; Plasma immunoreactive endothelin-1 concentrations were determined by radioimmunoassay in 11 septic patients during the first 24 hours after the development of the sepsis syndrome in 15 nonseptic postoperative patients studied 24 hours after open heart surgery and in 14 healthy volunteers . Mean endothelin-1 plasma concentrations were significantly (p less than 0.001) increased in septic patients (19.9 +/- 2.2 pg/mL, mean +/- standard error) compared to concentrations found in postoperative cardiac patients (11.9 +/- 0.7 pg/mL) or in healthy volunteers (6.1 +/- 0.3 pg/mL) . In septic patients elevated plasma concentrations of endothelin-1 were inversely correlated with cardiac index (r = -0.80, p less than 0.005) and positively correlated the severity of illness as documented by APACHE II score (r = 0.74, p less than 0.01) and plasma creatinine levels (r = 0.80, p less than 0.005) . No such correlations were found in postoperative cardiac patients . These results indicate that endothelin-1 concentrations are correlated with the severity of illness and depression of cardiac output in patients with sepsis.

Arch Dis Child, 1991 Mar, 66(3), 335 - 7
Staff training: a key factor in reducing intravascular catheter sepsis; Puntis JW et al.; A children's hospital nutritional care team prospectively monitored the frequency of sepsis in central venous catheters used for administering parenteral nutrition . During an initial study period of 12 months, 26/58 (45%) of catheters were removed because of proved sepsis . The possible causes of this alarmingly high rate were examined, with catheter care techniques on the wards coming under particular scrutiny . As a result protocols were modified and an intensive staff training programme implemented throughout the hospital, led by the nutritional care sister . Subsequently, the catheter sepsis rate was significantly reduced with only 9/107 (8%) of consecutive catheters becoming infected . These findings emphasise the key role that education of staff plays in controlling central venous catheter sepsis and the importance and cost effectiveness of special nursing staff in implementing such measures.

Anesteziol Reanimatol, 1991 Mar-Apr, (2), 59 - 61
{Correction of the immunologic shifts induced by hemosorption in sepsis of the newborn}; Murav'ev OV et al.; Alongside with a positive clinical effect, hemosorption (HS) leads to the elimination of humoral immunity factors (Ig, FN) from the blood, having no effect on the phagocytic activity of leukocytes . Massive immunocorrection in doses 2-3 times higher than the age-matched ones, increases considerably the levels of IgG and FN . Immunomodulating effect of HS is enhanced when HS is combined with ultraviolet blood irradiation.

Clin Sci (Lond), 1991 Mar, 80(3), 213 - 7
Hepatic phosphofructokinase-1 activity and fructose 2,6-bisphosphate levels in patients with abdominal sepsis; Arnold J et al.; 1 . In sepsis various processes of carbohydrate metabolism, such as hepatic gluconeogenesis and glycolysis, are altered . Phosphofructokinase-1, a key glycolytic enzyme, is controlled in the long term via regulation of synthesis and degradation of the protein itself, while in the short term it is regulated by allosteric effectors, such as fructose 2,6-bisphosphate (the most potent) . In the present study hepatic phosphofructokinase-1 activity as well as phosphofructokinase-2 activity and the concentration of fructose 2,6-bisphosphate were assayed to determine if they might contribute to the derangement of carbohydrate metabolism seen commonly in sepsis . 2 . The levels of glycogen and fructose 2,6-bisphosphate and the activity of phosphofructokinase-1 and phosphofructokinase-2 were determined in hepatic biopsies obtained at laparotomy from six patients with and seven patients without abdominal septic foci . 3 . A significant increase in plasma lactate concentration was observed in the septic patients, whereas no significant differences in tissue glycogen content or plasma glucose concentration were seen between the groups . 4 . No significant change in plasma insulin concentration was observed . However, levels of the counter-regulatory hormones (glucagon, cortisol and adrenaline) were elevated in the septic patients . 5 . A 60% decrease in hepatic phosphofructokinase-1 activity was seen in the septic patients . However, no significant changes in hepatic phosphofructokinase-2 activity and fructose 2,6-bisphosphate content were observed in the septic patients . 6 . The present results demonstrate that the decrease in hepatic phosphofructokinase-1 activity occurring in sepsis does not appear to reflect alterations in the concentration of fructose 2,6-bisphosphate.

Rev Med Chil, 1991 Mar, 119(3), 262 - 6
{Plasma calcium levels in critical patients with and without sepsis}; Gallardo J et al.; We determined total plasma calcium levels in 44 critically ill patients without evidence of renal or hepatic failure, 25 of them with active systemic infection . Plasma Ca was 7.49 +/- 0.1 mg/dl in the septic group compared to 8.46 +/- 0.2 in non septic patients (p < 0.01) . Corresponding levels of serum albumin were 2.26 +/- 0.1 and 3.05 +/- 0.2 milligrams, respectively (p < 0.01) . Corresponding corrected plasma Ca levels were 9.19 +/- 0.1 and 9.39 +/- 0.1 mg/dl (NS) . No correlation of lactate and plasma Ca levels was found . Mortality was 56% for septic and 16% for non septic patients . Patients with hypocalcemia had 53% mortality rate compared to only 16% in normocalcemic patients . PTH levels were normal in all but one patients, thus ruling out a rapid installation secondary hyperparathyroidism . Hypoperfusion does not appear related to ionic Ca levels given the lack of correlation of Ca and lactate levels . Mortality is related to sepsis and hypoalbuminemia but not to corrected Ca plasma levels.

Am Surg, 1991 Feb, 57(2), 86 - 8
Effect of oxygen-free radical scavengers on survival in sepsis; Powell RJ et al.; Sepsis remains a leading cause of death in the surgical intensive care unit (SICU) patient following major surgery or trauma . Recent work has demonstrated that oxygen-free radicals (OFR) generated during sepsis contribute to the pathogenesis of this syndrome . The purpose of this study was to evaluate the effect of various new free radical scavengers on survival in sepsis . A total of 85 male Sprague-Dawley rats were placed into one of the following treatment groups . CONTROL: cecal ligation and puncture (CLP); PRE-AT: pretreatment with alpha-tocopherol (AT) 10 mg/100 gm SC x 3 days, and 5 mg/100 gm IV prior to CLP; AT: 20 mg/100 gm at time of CLP and 4 hours following CLP; U74006F: (21-aminosteroid which inhibits lipid peroxidation) 3 mg/kg IV at the time of and 4 hours following CLP; U78517F: (alpha-tocopherol analogue) 3 mg/kg at the time of and 4 hours following CLP . Survival was determined at various time points up to 72 hours . Pretreatment with AT resulted in improved survival, whereas the novel OFR scavengers U78517F and U74006F significantly improved survival and were efficacious without pretreatment . It was concluded that OFR scavengers can improve survival in sepsis.

Arch Surg, 1991 Feb, 126(2), 236 - 40
Effects of high-dose IgG on survival of surgical patients with sepsis scores of 20 or greater; Dominioni L et al.; Sixty-two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater (day 0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or human albumin (controls; 33 patients), repeated on days +1 and +5, in a prospective, double-blind, multicenter study . The two groups were similar in age, initial sepsis scores, and acute physiology and chronic health evaluation II score . A significantly lower mortality was recorded in the IgG-treated group (38%) than in controls (67%) . Septic shock was the cause of death in 7% of IgG-treated patients and in 33% of controls . The results of this study indicate that high-dose IgG improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater.

Arch Surg, 1991 Feb, 126(2), 219 - 24
Hepatic extraction of indocyanine green is depressed early in sepsis despite increased hepatic blood flow and cardiac output; Wang P et al.; Although active hepatocellular function is depressed during sepsis, it is not known whether this occurs in the very early stages of sepsis and whether it is due to depressed cardiac output or hepatic blood flow . To study this, rats were subjected to sepsis by cecal ligation and puncture and hepatocellular function was determined at various intervals thereafter by assessing the ability of the liver to clear different doses of indocyanine green . The indocyanine green concentration was continuously measured in vivo with a fiberoptic catheter and an in vivo hemoreflectometer . Maximal velocity and kinetic constant of the clearance of indocyanine green, hepatic blood flow, and cardiac output were determined in experimental and sham-operated rats . The results demonstrate that hepatic blood flow and cardiac output increased 2 to 10 hours after cecal ligation and puncture, while hepatocellular function (maximum velocity and kinetic constant) was decreased even 2 hours following cecal ligation and puncture . No linear correlation between hepatocellular function and hepatic blood flow or cardiac output was found under such conditions . The extremely early depression in active hepatocellular function, despite the increased hepatic blood flow and cardiac output, may form the basis for cellular dysfunctions leading to multiple organ failure during sepsis.

Arch Surg, 1991 Feb, 126(2), 170 - 5
Pneumonia complicating abdominal sepsis . An independent risk factor for mortality; Mustard RA et al.; Nosocomial pneumonia (NP) is associated with a significant mortality, 66% in a previous retrospective study of NP complicating intra-abdominal sepsis (IAS) . We prospectively compared the outcome of NP complicating IAS with that of recurrent IAS (R-IAS) in the absence of NP . Data were collected prospectively on 300 patients with IAS; 34 patients who presented with pneumonia were excluded from the analysis (44% mortality) . One hundred seventy-one patients with no NP and no R-IAS (group 1) had a hospital mortality of 20% (34 patients); 36 without NP in whom R-IAS developed (group 2) had a 17% mortality (six patients); and 47 with NP but no R-IAS (group 3) had a 53% mortality (25 patients) . Finally, 12 patients who had both NP and R-IAS suffered a 75% mortality (nine patients) . We examined the relationships among the following putative risk factors and mortality: APACHE (acute physiology and chronic health evaluation) II score (at initial presentation with IAS), the need for mechanical ventilatory assistance following initial treatment for peritonitis, steroid requirement, generalized peritonitis vs abscess, and the need for surgical as opposed to percutaneous treatment . Using mortality as the dependent variable, group 2 vs 3 as the explanatory variable, and the risk factors as confounders, logistic regression analysis indicated that the group difference was significant after controlling for confounders . We conclude that NP complicating IAS is an independent risk factor associated with a significant mortality compared with R-IAS . These data challenge the notion that death in IAS is usually due to recurrent or persistent intra-abdominal infection.

Am J Surg, 1991 Feb, 161(2), 266 - 71
Cytokines and glucocorticoids in the regulation of the "hepato-skeletal muscle axis" in sepsis; Fischer JE et al.; Sepsis results in muscle catabolism and peripheral release of amino acids with a concomitant uptake of amino acids in liver and acute-phase protein synthesis . In addition, there appears to be a cytokine-induced process that blocks muscle amino acid uptake in sepsis, further diverting amino acids from the periphery to the liver . In this article, evidence that cytokines and glucocorticoids play an important role in the regulation of hepatic and muscle protein metabolism during sepsis is presented.

Anaesthesist, 1991 Feb, 40(2), 85 - 91
{The mechanism of the reduction of protein catabolism following trauma and during sepsis using xylitol}; Georgieff M et al.; Total parenteral nutrition (TPN) after trauma and sepsis has two major goals . One is the reduction of enhanced protein catabolism; the second is the avoidance of enhancement of whole-body glucose turnover . Glucose and xylitol differ in their quantitative utilization rate after trauma and sepsis . Maximal glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled . In order to investigate whether these differences are associated with beneficial effects with regard to whole-body glucose turnover rate of gluconeogenesis and protein sparing, we conducted two studies using animal models and two clinical studies . METHODS . For the determination of glucose and protein turnover, radioactive and stable isotope techniques were applied . In an animal model a primed constant infusion of 3-H-6-glucose, 14-C-1-alanine and 13-C-3-alanine and 14-C-U-acetate was used to determine total glucose appearance, gluconeogenesis from 3-C-precursors and alanine flux . In the human studies hepatic glucose production was determined by using a primed constant infusion of 6.6-D-2-glucose and urea synthesis rate was determined by a primed constant infusion of 2-N-15-urea . RESULTS . In the first rat model we were able to show that hypocaloric xylitol compared to glucose significantly reduced whole-body glucose turnover from 1741 +/- 232 mumol/h during glucose infusion to 449 +/- 49 mumol/h during xylitol infusion and gluconeogenesis from C-3 carbons form 382 +/- 24 mumol/h during glucose infusion to 155 +/- 39 mumol/h during xylitol infusion after a burn trauma . In a second septic rat model the exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated N-balance from +144 +/- 90 mgN/kg body weight per day during glucose infusion to +699 +/- 80 mgN/kg body weight per day during glucose-xylitol infusion and a reduced 3-methyl-histidine excretion from 7.14 +/- 0.61 mumol/kg body wt . per day during glucose infusion to 4.10 +/- 0.56 mumol/kg per day during glucose-xylitol infusion, respectively . In two studies with surgical intensive care patients we were able to confirm the nitrogen-sparing properties of xylitol infusion, together with amino acids during hypocaloric feeding or during TPN with a glucose/xylitol mixture in a proportion of 1:1 . From a basal urea production rate of 9.2 +/- 1.6 mumol/kg min . xylitol led to a significant reduction with 6.4 +/- 1.5 mumol/kg per min . Hepatic glucose production was significantly reduced during xylitol infusion from basal 4.8 +/- 0.6 mg/kg per min to 3.1 +/- 0.7 mg/kg per min, respectively . Equicaloric glucose in a dosage of 3 g/kg per day had no effect . During TPN glucose/xylitol, in a proportion of 1:1 at a total dosage of 0.24 g/kg per h, significantly reduced whole-body glucose turnover, endogenous glucose production and lactate concentrations compared to an isocaloric glucose infusion . DISCUSSION . In animal as well as in human studies hypocaloric xylitol as well as a glucose-xylitol mixture were more efficient in preserving body protein than glucose alone . Whole-body glucose turnover was significantly reduced during hypocaloric xylitol or glucose-xylitol infusion compared to isocaloric glucose infusion . During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg body wt . per day using xylitol . During long-term TPN, a glucose-xylitol mixture in a proportion of 1:1 in a dosage of 3 g/kg body wt . per day each is recommended as energy source, together with amino acids and, if necessary, lipids.

Thromb Haemost, 1991 Jan 23, 65(1), 32 - 9
Quantification of functional and inactivated alpha 2-macroglobulin in sepsis; Abbink JJ et al.; Alpha 2-macroglobulin (alpha 2 M) in vitro inhibits numerous proteinases that are generated during inflammatory reactions and therefore, probably plays an important role in diseases such as sepsis . To monitor the state of alpha 2 M in sepsis, we developed novel assays for functional and inactive alpha 2M . Functional alpha 2M in plasma was measured by quantitating the binding of alpha 2M to solid-phase trypsin . Inactive alpha 2M (i alpha 2M) was assessed with a monoclonal antibody, mcAb M1, that specifically reacts with a neodeterminant exposed on i alpha 2M . This mcAb in combination with chromogenic substrates was used to detect alpha 2M-proteinase complexes . Functional alpha 2M was reduced in plasma from 48 patients with clinical sepsis compared to healthy controls (p less than 0.0001) . Levels of functional alpha 2M on admission and the lowest levels encountered in 23 patients with shock were lower than in 25 normotensive patients (p = 0.023 and p = 0.009, respectively) . Increased levels of i alpha 2M (greater than 30 nM) at least on one occasion were found in only 4 of the 48 patients, being not different in hypotensive compared with normotensive patients, and not in patients who died compared with those who survived . Levels of functional alpha 2M correlated significantly with levels of factor XII and prekallikrein suggesting that decreases in alpha 2M at least in part were due to contact activation . Indeed, in two patients with increased i alpha 2M, complexes between alpha 2M and kallikrein were demonstrated in addition to plasmin- and thrombin-alpha 2M complexes.

Rev ADM, 1991 Jan-Feb, 48(1), 45 - 51
{Death from generalized sepsis of dental origin . Contribution to clinical casuistry}; Ocampo Flores P et al.; The presentation of the Death by generalized sepsis of dental origen has the purpose to aid the dental practitioner in the fields of diagnosis, etiologi, treatment and evolution in other cases with similar situations where a better diagnosis can give a better chance for survival in similar circumstances.

Klin Khir, 1991, (1), 27 - 30
{Complex correction of intoxication syndrome in sepsis}; Torbinskii AM; The experience with treatment of 120 patients with endotoxicosis caused by sepsis of different etiology is summarized . In the complex of treatment, the endolymphatic therapy, application, gastrointestinal sorption, hemosorption, plasmapheresis, plasmosorption, ultraviolet irradiation of the blood were used.

Ann Med Interne (Paris), 1991, 142(2), 91 - 4
{TNF and sepsis}; Durocher A et al.; Recent experiments have demonstrated that TNF plays an important role in the pathogenesis of septic shock . To confirm the involvement of TNF in human septic shock, serum TNF levels were measured in 10 adult patients admitted to the intensive care unit for sepsis with or without shock . Septic shock was corroborated by hemodynamic data (right catheterization, measurement of cardiac output by thermodilution) . For TNF measurement, venous blood samples were withdrawn, as soon as possible after the onset of sepsis, into a pyrogen--free tube . Serum TNF levels were determined using a radioimmunoenzymatic assay (IRE Medgenix) . During septic shock (n = 7), TNF levels were significantly higher (m = 354 +/- 131 pg/ml) than during sepsis without shock (n = 8; m = 145 +/- 35 pg/ml) (p less than 0.0005) . TNF levels were also significantly higher in non-survivors (m = 392 +/- 111 pg/ml) than in survivors (m = 167 +/- 81 pg/ml) (p less than 0.0005) . The value of 250 pg/ml seems to be critical: no patient without shock had TNF levels above 250 and all the patients who died early during the first 24 h) had TNF levels above 250 . The TNF level is negatively correlated with the platelet count (r = -0.70; p less than 0.05) . These data favor a pathophysiological for TNF in human sepsis and septic shock.

Indian Pediatr, 1991 Jan, 28(1), 39 - 43
Exchange transfusions in neonatal sepsis; Dalvi R et al.; Between October, 1987 and October, 1988, 53 neonates with severe or unresponsive sepsis were subjected to therapeutic exchange transfusions (ET) using 170 ml/kg of citrated blood less than 24 hours old . The procedure was repeated up to a maximum of 4 times . The success of therapy was adjudged by resolution of sclerema and/or improvement in clinical features . There were 32 low birth-weight (LBW) and 21 non-LBW infants and 51/53 subjects had sclerema . The mean time for recovery following ET was 19.6 +/- 12.4 h (range: 1-48 h) . The overall survival was 77.4% and the survival rates for LBW and non-LBW infants were 73.6 and 68.2%, respectively, however, the difference was not statistically significant . No significant or fatal complications occurred during ET . The effects of other associated problems on outcome studied by multiple regression analysis showed that neurologic problems were associated with a poor chance for survival despite ET . Exchange transfusion may thus be an effective and safe therapeutic modality for severe neonatal sepsis.

J Laryngol Otol, 1991 Jan, 105(1), 1 - 6
Patrick Watson-Williams and the concept of focal sepsis in the sinuses: an historical caveat for functional endoscopic sinus surgery; Fairley JW; From 1900 to 1940 the theory of focal sepsis was invoked to justify a number of dubious surgical procedures . Surgeons believed they were acting rationally . Patrick Watson-Williams advocated suction exploration of the paranasal sinuses for mental patients, claiming to cure criminal insanity by sphenoidotomy . Favourable contemporary reviews showed international approval . The rational basis of treatment was emphasised, but there was little systematic evaluation of outcome . Current enthusiasm for functional endoscopic sinus surgery is also based on a rational approach, logical deductions from pathophysiological 'facts' . Outcome has still not been evaluated scientifically . We should learn from history . Treatment should not be based too readily on what seems to be rational now . Ideas of physiology and pathology change . What seems logical today may appear ridiculous tomorrow . Careful analysis of outcome, preferably by controlled clinical trials, is needed as a rational treatment requires empirical validation just as much as any other.

Isr J Med Sci, 1991 Jan, 27(1), 52 - 60
Role of tumor necrosis factor in the pathogenesis of intravascular coagulopathy of sepsis: potential new therapeutic implications; Aderka D; Tumor necrosis factor (TNF) induced by bacterial lipopolysaccharide (LPS) was shown to have an important role in precipitation of septic shock and disseminated intravascular clotting (DIC) . At the endothelial level TNF down-regulates thrombomodulin (thus preventing protein C formation) and inhibits the production of tissue plasminogen activator (t-PA), thus impairing anticoagulant mechanisms . On the other hand, TNF up-regulates the production of procoagulant factors such as t-PA inhibitor (PAI), tissue factor and platelet activating factor (PAF) . These effects create an imbalance between procoagulant and anticoagulant mechanisms, in favor of the former . TNF also activates polymorphonuclears (PMNs), and increases their chemotaxis and adherence to endothelial surfaces by up-regulation of specific endothelial (ELAM-1) and PMN (CDw18) adherence proteins . The damage inflicted by activated PMN to the endothelial cell promotes tissue factor exposure and PAI release, with initiation of the characteristic explosive coagulation process of DIC, facilitated by the dissociation between pro- and anticoagulant mechanisms induced by TNF . These newly discovered mechanisms precipitating septic shock and DIC enable consideration of new treatments for this condition as anti-TNF antibodies or TNF inhibitors, anti-ELAM-1 antibodies anti-tissue factor antibodies, administration of activated factor C, etc . These therapeutic approaches may revolutionize the treatment of septic shock and DIC in the next decade.

Life Sci, 1991, 48(7), 603 - 11
Depletion of rat liver glucocorticoid receptor hormone-binding and its mRNA in sepsis; Ali M et al.; Glucocorticoid receptor (GR) hormone-binding activity, its physical characteristics, and GR mRNA levels were studied in the liver, brain and muscle of normal (saline-injected) and hypermetabolic septic rats 24 h after the subcutaneous injections of E . coli . The GR levels (hormone-binding activity) declined by about 40%, 56%, and 40% in septic liver, brain, and muscle cytosol, respectively . The mechanism of the decrease in the GR levels in sepsis was studied in liver . The GR levels remained low (45% of control hormone-binding) even after 48 h of E . coli administration . The decrease in the liver GR occurred in the 9S untransformed GR . The 9S GR from septic liver transformed to the 4S form in proportions comparable to the control liver GR . In addition, the 4S GR from control and septic liver was capable of binding to DNA-cellulose to a similar extent . The GR mRNA level in septic liver declined by about 30% . Thus, a decrease in GR hormone-binding activity in sepsis appears to be due to a decline in the steady-state GR mRNA level and not from a change in the qualitative properties of the GR protein.

Am J Physiol, 1991 Jan, 260(1 Pt 1), C50 - 7
Sepsis does not impair tricarboxylic acid cycle in the heart; Hotchkiss RS et al.; Sepsis has been reported to cause mitochondrial dysfunction and inhibition of key enzymes that regulate the tricarboxylic acid (TCA) cycle . We investigated the effect of sepsis on high-energy phosphates, glycolytic and TCA cycle intermediates, and specific amino acids that are involved in regulating the size of the TCA cycle pool during changes in metabolic state of the heart . Sepsis was induced in 12 female rats by the cecal ligation and perforation technique under halothane anesthesia; seven control rats underwent cecal manipulation without ligation . At 36-42 h postsurgery, the rats were reanesthetized, the chest was opened, and the hearts were freeze-clamped . Perchloric acid extracts of the hearts were analyzed with fluorometric enzymatic methods and 31P nuclear magnetic resonance spectroscopy . There were no significant differences in the levels of the TCA cycle intermediates or high-energy phosphates between the septic and control rats . The major metabolic changes were the 28% decrease in alanine and the 31% decrease in glutamate in the septic hearts compared with control (P less than 0.05 and P less than 0.005, respectively) . Phosphocholine, a component of membrane phospholipids, was increased by 91% in the septic hearts (P less than 0.01) . We conclude that sepsis does not impair the TCA cycle or induce significant cellular ischemia in the heart . The increase in phosphocholine may represent significant cellular membrane disruption during sepsis.

Nurs Res, 1991 Jan-Feb, 40(1), 36 - 41
Premature rupture of the membranes and sepsis in preterm neonates; Levine CD; This investigation was designed as a historical cohort study using data abstracted from medical records . Five hundred seven preterm neonates (26-35 weeks gestation) born alive from singleton pregnancies complicated by premature rupture of the membranes (PROM) were selected . Each neonate was matched on gestational age, gender, ethnicity, and date of delivery to a neonate without PROM . A matched pairs analysis was done using risk ratios (RR) to measure strength of the association and risk differences (RD) to measure absolute effect . Analysis revealed that preterm births complicated by PROM were at significantly higher risk of neonatal sepsis (RR = 3.5) and infection (RR = 2.4) . The RDs indicated that PROM exposure contributed an excess of 5 cases of sepsis per 100 infants (RD = 0.05) . PROM was not significantly associated with neonatal mortality, but when PROM had existed over 48 hours there was a higher risk of sepsis and infection . Birth of a neonate over 1500 grams or 33 weeks gestation was the most important factor in reducing risk of infection in PROM deliveries.

J Surg Res, 1991 Jan, 50(1), 51 - 6
Palmitate and stearate kinetics in the rat during sepsis and trauma; Cardwell RJ et al.; Kinetics of plasma free palmitate and stearate were measured in control and septic-traumatized rats to determine the contribution plasma free fatty acids make to increased resting energy expenditure . Measurements were made at 24 hr after insult using a primed, 4-hr continuous infusion of selected (1-14C) fatty acid . The plasma concentration of palmitate was increased and stearate was decreased in sepsis-trauma rats compared to plasma concentrations in healthy control rats . Fatty acid turnover rates during sepsis-trauma were changed from control turnover rates in the same direction as plasma concentrations . Oxidation rates for palmitate and stearate at 24 hr after induction of sepsis-trauma were not different from oxidation rates in control rats . Plasma free fatty acids were concluded not to exhibit increased oxidation after sepsis-trauma and not to contribute extra energy during hypercatabolism . This finding contrasts with glucose and amino acids which have an increased oxidation rate during hypercatabolism.

Arch Surg, 1991 Jan, 126(1), 28 - 32
Organ interactions in sepsis . Host defense and the hepatic-pulmonary macrophage axis; Callery MP et al.; Endotoxin (lipopolysaccharide {LPS}) and tumor necrosis factor (TNF-alpha) have been implicated in the pathogenesis of sepsis-induced adult respiratory distress syndrome . To evaluate the possible interaction of the hepatic-pulmonary macrophage axis in the adult respiratory distress syndrome, we compared the kinetics of immunosuppressive prostaglandin E2, TNF-alpha, and interleukin 6 production in LPS-stimulated Kupffer cells and alveolar macrophages (AMs) . Interleukin 6 production by Kupffer cells was significantly higher than for equal numbers of AMs . Kupffer cell TNF-alpha levels peaked early before decreasing as regulatory prostaglandin E2 levels rose . In contrast, AM TNF-alpha levels rose sharply and remained significantly higher than for Kupffer cells throughout culture coincident with negligible prostaglandin E2 production . Kupffer cell sequestration of LPS may normally invoke a coordinated cytokine response able to locally induce acute-phase hepatocytes . In hepatic failure, however, LPS spillover to the lung may promote adult respiratory distress syndrome by inducing unregulated AM TNF-alpha production within the pulmonary microenvironment.

Chest, 1991 Jan, 99(1), 224 - 9
Rabbit skeletal muscle PO2 during hypodynamic sepsis; Gutierrez G et al.; We measured skeletal muscle tissue PO2 (PtO2) in anesthetized rabbits (n = 7) following infusion of an intravenous bolus of E coli endotoxin . An array of surface PO2 microelectrodes was placed over the hindlimb biceps femoris muscle and sufficient readings were obtained to construct a PtO2 histogram . Changes in the histogram standard deviation were used to characterize micro-circulatory maldistribution . Systemic O2 consumption (VO2) was measured by the expired gas method . Cardiac output (Q) and systemic O2 transport (TO2) were calculated . Samples of arterial, right atrial (ra), and hindlimb venous blood, from a catheter placed in the infrarenal portion of the vena cava, were simultaneously obtained for measurement of blood gases and saturations . Following the administration of endotoxin, there were decreases in Q and TO2 of approximately 50 percent . The VO2 initially decreased 23 percent, but returned to baseline levels 30 minutes after endotoxin administration . Systemic O2 extraction ratio (ERO2 = VO2/TO2) increased from 0.32 +/- .03 to 0.54 +/- .07 (p less than 0.01), whereas hindlimb ERO2 increased from 0.42 +/- .03 to 0.60 +/- .02 (p less than 0.01) . The arithmetic mean of the PtO2 histograms decreased after endotoxin infusion (43 +/- 4 to 7 +/- 2 mm Hg; p less than 0.01), but PLO2 remained at baseline levels (35 +/- 2 vs . 33 +/- 2 mm Hg; p = NS) . The standard deviation of the PtO2 histograms remained constant during the experiment . This finding supports the notion that skeletal muscle microcirculatory heterogeneity does not increase during endotoxin induced hypodynamic sepsis.

J Infect Dis, 1991 Jan, 163(1), 83 - 8
Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular and peritonitis models of sepsis; Bagby GJ et al.; The role of tumor necrosis factor-alpha (TNF alpha) in the lethal consequences of intravascular lipopolysaccharide (LPS) or Escherichia coli sepsis was compared with that in bacterial peritonitis . Intravenous administration of E . coli LPS or E . coli (live or dead) resulted in large transient increases in serum TNF alpha levels, peaking at 90 min at 10,000-30,000 units/ml . In contrast, the serum TNF alpha response following the induction of bacterial peritonitis was substantially less, peaking at 200-500 units/ml . Sterile peritonitis (essentially nonlethal) and bacterial peritonitis (greater than 60% lethal) elevated TNF alpha levels to 1000-2000 units/lavage within the peritoneal cavity 2 h after challenge . Passive immunization with neutralizing goat anti-TNF alpha IgG improved survival from 8% to 75% in rats administered LPS intravenously but was completely ineffective in protecting rats from lethal E . coli peritonitis . Thus significant differences exist in the role TNF alpha plays in systemic intravascular models of sepsis and bacterial peritonitis.

Int Urol Nephrol, 1991, 23(5), 485 - 8
Sepsis caused by periurethral abscess; Malatinsky E; The author presents an unusual case of general sepsis of the organism caused by periurethral abscess in a 38 years old man . The aetiology is discussed.

Comput Biol Med, 1991, 21(3), 143 - 59
A basic program for calculation of APACHE II and Elebute scores and sepsis evaluation in intensive care medicine; Pilz G et al.; This paper describes a program for bedside-practicable calculation of APACHE II score, providing an additional option for both a rapid and sensitive screening as well as for a more specific sepsis assessment by the Elebute score in case of a putative diagnosis of sepsis . Thus, diagnostic and prognostic evaluation of septic patients and the assessment of disease progression and classification of "responders" to therapy can be promptly available in the ICU setting . The program is written in BASIC and therefore can easily be adapted to most microcomputers available on the market.

Sov Med, 1991, (5), 27 - 8
{HBO in the combined therapy of purulent peritonitis and peritoneal sepsis}; Lukich VL et al.; The study was made of HBO effect on changes of biologic fluid toxicity in purulent peritonitis . HBO was introduced in combined therapy of 68 patients (32 with general peritonitis and 36 with peritoneal sepsis) . Lethality in peritonitis patients reached 40.6% (19 patients), in sepsis patients 33.3% (12 patients).

Arkh Patol, 1991, 53(3), 53 - 8
{Sepsis and local inflammatory processes in infants: mathematical approach to pathomorphological differential diagnosis}; Barsukov VS; The structure of thymus, spleen, adrenal and thyroid glands and changes in peripheral white blood cells formula were studied in 97 cases of sepsis and local inflammatory processes (LIP) in infants . A complex of differential diagnostic features of sepsis and LIP was defined . Mathematical use of the complex significantly increases the objectivity of sepsis and LIP diagnosis.

Am Rev Respir Dis, 1991 Jan, 143(1), 155 - 61
Sepsis-induced lung injury and the effects of ibuprofen pretreatment . Analysis of early alveolar events via repetitive bronchoalveolar lavage; Jenkins JK et al.; Current knowledge of alveolar pathophysiology during early sepsis-induced acute lung injury (ALI) and the role of resident alveolar macrophages (AM) in mediating alveolar inflammatory events during sepsis is limited . Further, the effects of ibuprofen pretreatment upon alveolar pathophysiology and AM function during early sepsis-induced ALI is unclear . Utilizing repetitive bronchoalveolar lavage (BAL) in a porcine model of sepsis-induced ALI, we studied changes in alveolar cellular constituents, BAL protein content and molecular composition, and AM superoxide anion (O2-.) generation during early sepsis . The neutrophil percentage of recovered alveolar cells (17 +/- 8%, t = 300 min versus 2 +/- 1%, t = 0; p = 0.06) and the bronchoalveolar lavage total protein content (493 +/- 110 micrograms/ml, t = 300 min versus 109 +/- 18 micrograms/ml, t = 0; p less than 0.05) increased in septic animals . Increases in BAL fluid total protein were primarily due to low-molecular-weight plasma protein, indicating relative preservation of alveolar-capillary membrane size selectivity . Alveolar macrophages harvested following 300 min of sepsis generated significantly less O2- . following phorbol myristate acetate (PMA) stimulation compared to AM harvested at baseline . Ibuprofen pretreatment of septic animals completely blocked leakage of plasma proteins into the alveoli and attenuated neutrophil migration but did not prevent downregulation of AM O2- . generation . Increased alveolar-capillary membrane permeability, neutrophil migration into the alveoli, and downregulation of AM oxidant generation occur within hours of the onset of sepsis . Ibuprofen pretreatment significantly attenuates early sepsis-induced ALI without altering sepsis-induced AM dysfunction.

Chest, 1991 Jan, 99(1), 176 - 84
Peripheral nerve function in sepsis and multiple organ failure; Witt NJ et al.; Forty-three patients who had sepsis and multiple organ failure (critical illness) were studied prospectively to determine the incidence and severity of peripheral nerve function and to correlate such function with a number of variables . Electrophysiologic studies indicated a primary axonal degeneration of motor and sensory fibers in 30 (70 percent) . Fifteen (30 percent) had the clinical signs of difficulty in weaning from assisted ventilation, weakness of limb muscles, and reduced or absent deep tendon reflexes . Full recovery from the polyneuropathy occurred among the 23 (53 percent) who survived, except three who had a very severe polyneuropathy . A peripheral nerve function index, computed from electrophysiologic measurements, showed statistically significant (p less than 0.01) negative correlations with the time in the critical care unit, and the serum glucose value; the serum albumin level showed a positive correlation . Multiple regression analyses indicated all three factors accounted for 47 percent (r2 = 0.4678) of all potential variables . In a separate analysis, the nerve function index correlated with the amplitude of the diaphragm compound muscle action potential (p less than 0.01) . The results were consistent with the polyneuropathy being due to the same mechanisms that are currently postulated to cause dysfunction in this syndrome of other organ systems (including the neuromuscular respiratory system).

Vestn Akad Med Nauk SSSR, 1991, (5), 41 - 4
{Morphology of sepsis in young children}; Stepanov SA; The paper outlines early childhood sepsis as a systemic infectious disease acyclically proceeding in the presence of alterations in the body reactivity, analyzes the autopsy specimens obtained from over 200 infants who died from various sepsis types in the period of 1965-1989, describes the morphofunctional features of sepsis in infants, and yields a concept that immunodeficiency contributes to the disease.

Ter Arkh, 1991, 63(11), 74 - 7
{Efferent therapy in the combined treatment of sepsis}; Neimark II et al.; Efferent therapy (hemosplenosorption, plasmapheresis, autologous blood radiation) was used in multimodality treatment of 45 patients with sepsis . The therapy exerted a beneficial effect on the disease, favoured the elimination of or minimized intoxication, normalized hemostasis and immunity . Indications for use of hemosplenosorption, plasmapheresis and autologous blood radiation are provided.

Klin Khir, 1991, (12), 24 - 6
{The extracorporeal connection of a donor spleen in the treatment of anaerobic sepsis}; Rotar' VI et al.; In 12 patients with anaerobic sepsis, extracorporeal connection of donor spleen, its sections and transfusion of perfusates of xenospleen were used in the complex treatment . A positive result--reduction of intoxication, improvement of general state, normalization of immunologic indices--has been obtained.

Soc Sci Med, 1991, 33(12), 1385 - 90
The application of operational research (OR) procedures to maternal mortality from puerperal sepsis in a rural community; Adetoro OO et al.; An operation research (OR) procedure on maternal mortality from puerperal sepsis was carried out in Irepodun Local Government Area of Kwara State of Nigeria . The study involved ten focus groups discussion (FGD) in two districts of the Local Government Area . The findings were analysed from three broad perspectives, that is, consumers' views, providers' views and community decision takers' views . In general, the analysis revealed that the community knowledge of puerperal sepsis is poor . In addition, limited access and prohibitive cost of orthodox health care services prevented the community from full utilization of the few available health care centres in the community . The study also revealed that there is urgent need to introduce three key interventions for an improved maternity care in the community . These interventions are community health education, health institutions development and community participation in provision of ancillary services such as transportation.

J Arthroplasty, 1991, 6 Suppl, S47 - 51
Incidence of deep sepsis in total hip arthroplasty . Survivorship analysis over 17 years from one hospital; Schmalzried TP et al.; Of 3,051 total hip arthroplasties (THA) performed between January 1970 and August 1986, 47 hips in 43 patients developed deep periprosthetic infection . This population was divided temporally into three groups based on changes in our perioperative antiseptic technique . Using survivorship analysis, a significant decrease in the sepsis rate in primary THA was seen in the period since 1974 (P less than .03) . Comparing all surgeries in the most recent cohort (1980-1986) to others by a Cox Proportional Hazards model (which accounts for differences in follow-up results), indicates that the relative risk of sepsis has decreased by half in this latest group . Contemporary perioperative antiseptic techniques have lowered the risk of infection in THA . Further significant decreases in sepsis incidence will likely require a reduction in the incidence of infection acquired outside the operating room.

Res Exp Med (Berl), 1991, 191(3), 177 - 87
Enhancement and hepatocyte-modulating effect of chemical mediators and monokines produced by hepatic macrophages in rats with induced sepsis; Monden K et al.; We investigated the production of chemical mediators by hepatic macrophages from rats with sepsis and the modulation of hepatocyte function by these hepatic macrophages . The chemical mediators we measured were superoxide (O2-), TNF, IL-1, and PGE2 . Production of these mediators by hepatic macrophages from rats with sepsis was significantly increased . Furthermore, protein synthesis by cultured hepatocytes was inhibited in a co-culture system of hepatocytes and hepatic macrophages from rats with sepsis, and it was even inhibited by the supernatant of cultured hepatic macrophages from septic rats . These results demonstrate that hepatic macrophages are activated in sepsis and may play a role in inducing hepatic dysfunction in sepsis.

Clin Chim Acta, 1990 Dec 14, 193(3), 103 - 11
Polymorphonuclear elastase in neonatal sepsis; Tsaka T et al.; Quantitative analysis of polymorphonuclear elastase was carried out in 135 newborn infants during the first 28 days of life . In 15 neonates with septicaemia, significantly increased PMN-elastase activity (range 75 to 700 micrograms/l: P less than 0.0001) was observed at the time of recognition of infection . Cut-off level 65 micrograms/l . Normalisation of the elastase activities was observed only under real recovery of the patients . It is concluded that plasma elastase determination serves as a sensitive indicator of systemic infection in neonatology, and as a good parameter for monitoring the course of the disease, because PMN-elastase correlates with the clinical condition of the patient.

J Trauma, 1990 Dec, 30(12 Suppl), S192 - 7
Altered Ca2+ homeostasis and functional correlates in hepatocytes and adipocytes in endotoxemia and sepsis; Spitzer JA; Decreased cytosolic {Ca2+} and impaired Ca2+ release in response to an IP3 challenge are among perturbations in hepatocyte Ca2+ homeostasis associated with endotoxemia and sepsis . These changes are consistent with the accompanying alterations in appropriate physiologic functions, e.g., activation of glycogen phosphorylase and gluconeogenesis, mediated by {Ca2+}c and defective phosphorylation of relevant enzymes . Attenuation of IP3 binding to the subcellular fractions that are imputed to be targets of IP3 and a decrease in the size of the IP3-sensitive pool of releasable Ca2+ are underlying components of the mechanism of the reduced Ca2+ release upon IP3 stimulation and its metabolic sequelae . ET treatment leads to a significant increase in Ca2+ associated with the cell surface compartment of adipocytes, a reduction in 45Ca2+ uptake by endoplasmic reticulum and higher cytosolic {Ca2+} under basal conditions and upon ACTH stimulation than that observed in cells of control rats . The reduced 45Ca2+ uptake is also manifest in adipocytes of septic rats . Alterations in adipocyte metabolism induced by ET include increased oxidation of glucose to CO2 (an insulin-like effect) and increased lipolysis upon NE and ACTH stimulation.

Surgery, 1990 Dec, 108(6), 1097 - 101
Calcitonin gene-related peptide levels are elevated in patients with sepsis; Joyce CD et al.; Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator . Plasma levels of CGRP have been elevated in animal models with sepsis . This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis . Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis . Volunteers were afebrile and had normal pulse and blood pressure . Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities . CGRP was extracted and assayed by radioimmunoassay for iodine 125-labeled human CGRP . In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000) . Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005) . These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state.

Chest, 1990 Dec, 98(6), 1467 - 72
Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure; Pittet JF et al.; Inadequate tissue oxygenation may occur in critically ill patients with sepsis despite an apparently adequate O2 transport (QO2), and this may contribute to the development of an O2 debt and also to multiple organ failure . It has been shown that increasing QO2 by infusing a vasodilator may reveal this O2 debt in septic patients . To investigate whether the site of action of vasodilators may be of importance in unmasking such an O2 debt, we administered prostacyclin, a prostaglandin with a preferential effect on the microcirculation, and phentolamine, an arteriolar vasodilator, in 11 patients studied during the first 48 hours after the onset of sepsis, and compared their effect on whole body oxygen consumption (VO2) and skin microvascular blood flow . The results demonstrated that increasing QO2 by prostacyclin but not by phentolamine significantly increases VO2 in critically ill patients with sepsis . The site of action of vasodilators may therefore play an important role in their ability to unmask an O2 debt.

Br J Clin Pract, 1990 Dec, 44(12), 640 - 1
Life-threatening peripharyngeal sepsis with mediastinitis; Baker AR et al.; A case of life-threatening peripharyngeal sepsis with mediastinitis is described . The pathology, relevant anatomy and treatment are discussed and the literature is reviewed.

Thromb Res, 1990 Nov 15, 60(4), 321 - 30
The effect of heparin on multiple organ failure and disseminated intravascular coagulation in a sepsis model; Tanaka T et al.; In order to elucidate a possible role of hypercoagulability leading to disseminated intravascular coagulation (DIC) in the pathogenesis of multiple organ failure (MOF), unfractionated heparin and the related agents were administered to septic rabbits which manifest DIC and MOF . Administration of heparin resulted in prevention of thrombocytopenia, leukopenia and elevation of plasma bilirubin and creatinine . The morphological hepatic damage was also ameliorated by heparin . Similar favorable effects were obtained by the administration of low molecular weight heparin . Dextran sulfate prevented the hepatic damage to some extent without improvement on other parameters . No significant effect was observed by the administration of a synthetic thrombin inhibitor (MD805) . These results indicate that the favorable effect of heparin is due to its anticoagulant property, especially anti-Xa activity . Thereby, it is concluded that the hypercoagulable state leading to DIC is a prerequisite for the occurrence of MOF in sepsis.

Br J Addict, 1990 Nov, 85(11), 1495 - 6
Anatomical distribution of soft tissue sepsis sites in intravenous drug misusers attending an accident and emergency department; Stone MH et al.; Of 77,686 case records of attendance at an accident and emergency department during 1986, 488 (0.6%) contained documented evidence of intravenous drug misuse (IDM) . Clinical examination had revealed signs of soft tissue sepsis in 150 (31%) of these, the commonest sites being the wrist and forearm (31% of lesions), the antecubital fossa (19%), fingers and hand (14%) and thigh and groin (11%) . These data highlight the anatomical areas to which medical and nursing staff should pay particular attention when examining patients with a background of IDM . Conversely, the presentation of soft tissue sepsis in these sites should alert clinicians to the possibility of underlying IDM.

J Appl Physiol, 1990 Nov, 69(5), 1893 - 902
Failure of therapy with 2,3-dihydroxybenzoic acid to modify the course of sepsis-induced lung injury; Sharpe MD et al.; Oxidant-induced injury of the pulmonary microvasculature reportedly contributes to an increase in microvascular permeability and pulmonary hypertension, both of which are principal features of acute lung injury (ALI) . We tested the hypothesis that antioxidant therapy with 2,3-dihydroxybenzoic acid (DHB), initiated in awake sheep after the development of sepsis-induced ALI, would ameliorate the progression of these lesions . DHB has many actions that suggested to us the potential for demonstrating benefit in ALI complicating sepsis; it is a nontoxic hydroxyl-radical scavenger that also inhibits the cyclooxygenase pathway and acts as a weak iron chelator . In preliminary experiments, we demonstrated that pretreatment with DHB prevented an increase in mean pulmonary arterial pressure, plasma thromboxane A2, measured as its metabolite thromboxane B2, and lymph total protein clearance that otherwise followed an infusion of zymosan-activated plasma (ZAP) in sheep . In subsequent experiments, 12 additional sheep were rendered septic by cecal ligation and perforation . Twenty-four to 36 h after cecal ligation and perforation, an increase in lung microvascular permeability was confirmed, because pulmonary lymph flow had increased by 82% while the mean lymph-to-plasma total protein ratio was unchanged from baseline . At this point, six sheep were then treated with parenteral DHB and six with DHB vehicle for the subsequent 24 h . In contrast to the demonstrated benefit of DHB pretreatment in preventing ALI secondary to an infusion of ZAP, the progressive increase in lymph total protein clearance that complicated septic lung injury in the DHB vehicle group throughout this 24-h study period was not ameliorated in the DHB treatment group . However, DHB did prevent a modest increase in mean pulmonary arterial pressures that was demonstrated in the DHB vehicle group throughout this 24-h treatment period . Although pretreatment prevented ALI after a ZAP infusion, we conclude that DHB only incompletely modified disease progression when administered after the onset of sepsis-induced ALI because it ameliorated the pulmonary hypertensive response without concurrently modifying an increase in lung microvascular fluid flux.

Pediatr Infect Dis J, 1990 Nov, 9(11), 819 - 25
A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience; Gladstone IM et al.; Records have been kept prospectively in our institution since 1928 of all positive blood cultures taken from neonates . Using a modification of objective Centers for Disease Control criteria to define sepsis, we reviewed the records of all neonates with positive blood cultures for the years 1979 to 1988 inclusive and found 270 cases of sepsis . The sepsis rate for infants less than or equal to 30 days of age was 2.7 cases/1000 live births, with a mortality rate from sepsis of 15.9% . There was an increase in sepsis due to commensal species (CS) over the period (P less than 0.007) . The number of infants in the nursery who developed sepsis when more than 30 days of age also increased (P less than 0.002), as did the rate of sepsis from CS in this group (P less than 0.001) . Isolation of CS from the blood with fulfillment of the modified Centers for Disease Control criteria was associated with a 13.7% mortality rate, whereas isolation of CS without fulfillment was associated with a 4% rate (P less than 0.01).

J Surg Res, 1990 Nov, 49(5), 390 - 3
Donor-specific tolerance permits burn allografting without increased sepsis; Garrison JL et al.; Early excision and allografting of massive burns is beneficial . However, chronic immunosuppression, utilized to prolong allograft survival, increases the potential risk of infection . We have previously shown long-term skin allograft survival in mice with a 30% total body surface area (TBSA) burn by inducing donor-specific tolerance (DST) using only perigrafting administration of antithymocyte globulin (ATG) and donor bone marrow (DBM) . Chronic immunosuppression is avoided . This study tests whether induction of DST compromises host resistance to infection . Resistance to a septic challenge created by cecal ligation and puncture (CLP) 10 days after a 30% TBSA burn was investigated in the following groups of mice: {table: see text} Positive blood cultures were documented for 97% of mortalities . Burn excision and grafting significantly (P less than or equal to 0.05) decreased mortality . No increased mortality was seen in allografted mice receiving ATG or ATG and DBM compared to isografted mice receiving no immunosuppression . These studies suggest that skin allografting with DST may permit the benefits of burn excision without the risks of infection seen with chronic immunosuppression.

Clin Sci (Lond), 1990 Nov, 79(5), 483 - 90
Metabolic regulation of renal gluconeogenesis in response to sepsis in the rat; Ardawi MS et al.; 1 . The regulation of renal gluconeogenesis was studied in rats made septic by a caecal ligation and puncture technique . 2 . Blood glucose concentrations were not markedly different in septic rats, but lactate, pyruvate and alanine concentrations were markedly increased, compared with sham-operated rats . Conversely, blood ketone body concentrations were significantly decreased in septic rats . Both plasma insulin and glucagon concentrations were markedly elevated in response to sepsis . 3 . The maximal activities of glucose-6-phosphatase (EC 3.1.3.9), fructose-1,6-bisphosphatase (EC 3.1.3.11), pyruvate carboxylase (EC 6.4.1.1) and phosphoenolpyruvate carboxykinase (EC 4.1.1.49) were markedly decreased in kidneys obtained from septic rats, suggesting diminished renal gluconeogenesis . 4 . Renal concentrations of lactate, pyruvate and other gluconeogenetic intermediates were markedly elevated in septic rats, whereas those of acetyl-CoA and fructose 2,6-bisphosphate were decreased and unchanged, respectively . 5 . The rate of gluconeogenesis from added lactate, pyruvate and glycerol was decreased in isolated incubated renal tubules from septic rats . 6 . Sepsis decreased the arteriovenous concentration difference for glucose, lactate, and alanine . Septic rats showed decreased net rates of glucose production and net rates of removal of lactate and alanine as compared with sham-operated controls . 7 . It is concluded that the diminished capacity for renal gluconeogenesis in septic rats could be the result of changes in the maximal activities or regulation of key non-equilibrium gluconeogenic enzymes or both, but the effect of other factors (e.g . toxins) has not been excluded.

Crit Care Med, 1990 Nov, 18(11), 1201 - 3
Plasma alpha-atrial natriuretic peptide concentrations in acute respiratory failure associated with sepsis: preliminary study; Mitaka C et al.; Plasma alpha-atrial natriuretic peptide (alpha-ANP) concentrations were measured during mechanical ventilation in nine patients with acute respiratory failure (ARF) associated with sepsis . The relationships between alpha-ANP and pulmonary hemodynamic variables were examined . A total of 22 measurements of alpha-ANP and other variables were obtained . The mean plasma alpha-ANP concentration of 22 measurements was 120.1 +/- 79.8 pg/ml (normal 31.7 +/- 12.0, mean +/- SD) . Plasma alpha-ANP concentrations correlated with mean pulmonary artery pressure (MPAP) (r = .703, p less than .01) and pulmonary vascular resistance (PVR) (r = .606, p less than .01), but not with other variables . These findings suggest that alpha-ANP elevation may be related to the increases in MPAP and PVR in ARF associated with sepsis.

Rev Clin Esp, 1990 Nov, 187(8), 395 - 8
{Changes in the hypophyseal-thyroid axis and their prognostic value in sepsis}; Mangas-Rojas A et al.; The alterations in serum concentration of thyroxine (T4), tri-iodine-thyronine (T3), reverse tri-iodinetiroinine (rT3), thyrotropine (TSH and free thyroxine index (IT4L), are studied in 37 patients diagnosed of sepsis who were divided into two groups according to their evolution: Group A: 22 patients who evolved favourably, and Group B: 15 patients who died, as well as in 14 healthy controls; this was carried out in order to establish, on one hand, its prognostic value, and, on the other, which of these parameters is most useful in the evaluation of thyroid function in these patients . A decrease in serum T3 levels was observed in patients from both groups (p less than 0.001) which was accompanied by an increase in rT3 levels (p less than 0.001) and a decrease in It4L (p less than 0.001); No significant modifications were observed in T4 and TSH . On follow up of 12 patients from group A and 14 from group B, an increase in mean T3 concentration was observed (p less than 0.02) only in the first patient from both groups . The greatest discriminative efficacy of thyroid hormones study with an unfavorable sepsis evolution corresponded to a T3 value below 35 ng/dl.

Aust N Z J Obstet Gynaecol, 1990 Nov, 30(4), 347 - 50
Postabortal pelvic sepsis in association with Chlamydia trachomatis; Wein P et al.; Cervical swabs for Chlamydia trachomatis culture were taken from 527 women presenting for elective termination of pregnancy . Twenty-six patients (4.9%) harboured C . trachomatis; 21 (81%) of these were less than 25-years-old and 21 (81%) were nulliparas . Postoperative pelvic sepsis developed in 11.5% of chlamydia-positive women, in contrast to 3.6% of chlamydia-negative women . Consequently it is suggested that all patients, especially those younger than 25 years, presenting for termination of pregnancy or in whom an intrauterine device is to be inserted should be screened and have treatment commenced for C . trachomatis prior to the operative procedurePIP: Cervical swabs for Chlamydia trachomatis culture were taken from 527 women presenting for elective termination of pregnancy . 26 patients (4.9%) harbored C . trachomatis; 21 (81%) of these were less than age 25 and 21 (81%) of these were less than age 25 and 21 (81%) were nulliparous . Postoperative pelvic sepsis developed in 11.5% of chlamydia-positive women, in contrast to 3.6% of chlamydia-negative women . Consequently, it is suggested that all patients, especially those under age 25, presenting for termination of pregnancy or in whom an IUD is to be inserted should be screened and begin treatment for C . trachomatis prior to the operative procedure . author's modified

Anesteziol Reanimatol, 1990 Nov-Dec, (6), 40 - 1
{Changes in the amino acid spectrum pf the blood in patients with sepsis undergoing complex intensive therapy}; Spas VV et al.; Amino acid fund was studied during intensive therapy of 25 patients with sepsis . In 15 patients complex therapy involved detoxicating hemosorption (3-5 sessions) and in 10 patients hemosorption was supplemented by ultraviolet blood irradiation (5-10 sessions) . Complex therapy with hemosorption led to a decrease in plasma serine content . The amino acid fund of the whole blood changed insignificantly . There was a significant increase in leucine, isoleucine, threonine and phenylalanine levels . The introduction of ultraviolet blood irradiation into complex therapy of patients decreases a traumatic effect of sorption detoxication on blood cells and potentiates detoxicating effect.

Mikrobiyol Bul, 1990 Oct, 24(4), 336 - 43
{Antibiotic and specific immunoglobulin G in the treatment of E . coli sepsis in mice previously given steroids}; Bakir M et al.; Experimental E . coli sepsis was constituted in two groups of mice . One of the groups have been immunosuppressed by steroid therapy of ten days (group A) and the other group was normal (group B) . Ceftriaxone and Ig G, prepared by vaccinating rabbits with the same strain of E . coli, were used in therapy . The results of the therapy in both were compared . The mortality rate of mice on Ig G therapy was % 70 in group A and % 80 in group B and that on ceftriaxone therapy % 60 and % 50, respectively . The mortality rate was % 30 in both groups with Ig G + ceftriaxone therapy . There wasn't any significance between these . On this research, the treatment of antibiotic together with Ig G decreased the mortality rate . The statistical value of the mortality rate among the treatment groups was not found significant.

Anaesthesist, 1990 Oct, 39(10), 547 - 51
{Is TNF-alpha "ripe" for routine diagnosis in sepsis?}; Hammerle AF et al.; Mortality of the septic syndrome is around 40-60% and can rise to 100% if multiple organ failure (MOF) develops . It is generally assumed that the high mortality of sepsis can only be reduced by early diagnosis and prevention of subsequent MOF . The aim of our study was to investigate the validity of routine TNF-alpha determination for the diagnosis of septicemia and, in combination with clinical scoring systems {MOF score and Acute Physiological and Therapeutic Intervention Score (APATIS)}, to define a "therapeutic window" during which an anti-TNF-alpha agent could be applied with the greatest chance of success . METHODS . TNF-alpha serum levels were measured and APATIS and MOF scores were calculated daily in 87 ICU patients . TNF-alpha serum levels were determined by means of an immunoradiometric assay (TNF-alpha IRMA, Medgenix, Belgium) . Sepsis was diagnosed in 24 patients according to clinical criteria . To quantify the severity of sepsis, we set up the APATIS . The MOF score was used to assess the severity of MOF . Data were analyzed using the SAS software package (SAS Institute, Cary, N.C.) and are expressed as mean +/- SEM . RESULTS . The mean values of all sequential TNF-alpha determinations were significantly higher in the septic patients compared to the nonseptic patients (73.2 +/- 4.3 vs 8.5 +/- 0.4 pg/ml; P less than 0.01) . Similarly, the maximum TNF-alpha values were significantly higher in the septic group (156.9 +/- 26.5 vs 20.1 +/- 1.3 pg/ml; P less than 0.01) . To differentiate between sepsis and nonsepsis we set the cut-off point at a TNF-alpha serum level of 40 pg/ml and calculated a sensitivity of 70.8%, a specificity of 98%, and a diagnostic accuracy of 91.3% . None of the patients with a maximum TNF-alpha level above 250 pg/ml survived . Mortality was 80% above a maximum TNF-alpha serum concentration of 200 pg/ml, whereas only 40% of patients with a TNF-alpha maximum below 150 pg/ml died . The mean APATIS and MOF scores were significantly higher for septic than for nonseptic patients (APATIS: 20.3 +/- 0.5 vs 8.1 +/- 0.2 and MOF: 9.8 +/- 0.1 vs 4.6 +/- 0.1) . To differentiate between survival and nonsurvival, we set the cut-off point at 25 for APATIS and calculated a sensitivity of 79% and a specificity of 93% . At a MOF score of 8, the sensitivity was 89% and the specificity 82% . In our series cumulative mortality at a maximum MOF of less than 8 was 4% and at MOF greater than 10, 68% . We found an interval of 2.9 +/- 0.9 days between the time TNF-alpha serum levels first exceeded 40 pg/ml and the development of severe MOF (MOF greater than 10) in 13 patients . CONCLUSION . Sequential TNF-alpha serum level determinations are useful for the diagnosis and prognosis of septicemia . We found an interval of 3 days between rising TNF-alpha serum levels and the development of severe MOF . This latency may represent the "therapeutic window" during which an anti-TNF-alpha-agent, e.g., a monoclonal anti-TNF-alpha-antibody, could be applied as a therapeutic consequence.

Anaesthesist, 1990 Oct, 39(10), 525 - 9
{Noradrenaline in the "high output-low resistance" state of patients with abdominal sepsis}; Redl-Wenzl EM et al.; We investigated the impact of norepinephrine administration on hemodynamics, oxygen metabolism and renal function in patients in severe septic shock . PATIENTS AND METHODS . Twenty-six patients with extremely low resistance who were between 24 and 87 years of age were included in the study . In 7 patients, acute necrotizing pancreatitis and superinfection was diagnosed; 19 patients suffered from diffuse peritonitis . The entrance criteria for the study were: a mean arterial pressure (MAP) of below 60 torr or, in chronic hypertensive patients, a decrease in systolic pressure of more than 50 torr compared to previous values, despite volume optimization, and dopamine greater than 20 micrograms/kg per min and cumulative doses of dopamine/dobutamine greater than 30 micrograms/kg per min, respectively . Cases with tachycardia greater than 140/min were also included in the study even when the inotropic medication dose was lower . After registration of baseline values, dopamine was reduced to 2.5 micrograms/kg per min, and norepinephrine was administered starting at a dose rate of 0.05 micrograms/kg per min, until a MAP of greater than 60 torr could be maintained . RESULTS . Of the 26 patients investigated, 16 survived; 10 patients with persisting sepsis died due to multiple organ failure (mortality: 38.5%) . During the study period, a norepinephrine dosage ranging between 0.1 and 2 micrograms/kg per min was necessary to stabilize the arterial pressure . The mean dose rate was 0.3 micrograms/kg per min . The mean arterial pressure and systemic vascular resistance index showed a statistically significant increase of 30 and 20%, respectively, just after 1 h and distinctly remained above the initial values in the further course . The cardiac index remained constant or increased slightly . After 24 h a statistically significant increase in stroke volume and a decrease in heart rate could be observed . Creatinine clearance increased significantly from the control value of 73 +/- 48 ml/min to 114 +/- 37 ml/min after 48 h under norepinephrine treatment . O2-delivery and O2-consumption did not change significantly, although they showed a slight tendency to increase . CONCLUSION . When patients are in a septic high output-low resistance condition, particular attention must be paid to maintaining sufficient mean arterial pressures . Our results suggest that this essential goal can be achieved by norepinephrine . The mean arterial pressure and glomerular filtration rate improved markedly, and there was no evidence of bad effects such as an increased afterload on critical parameters like cardiac index, O2-delivery and O2-consumption.

Orthop Rev, 1990 Oct, 19(10), 895 - 900
Necrotizing myonecrosis and polymicrobial sepsis . The role of adjunctive hyperbaric oxygen; Topper SM et al.; A 19-year-old man, who was involved in a motorcycle accident, sustained a combined bony and vascular injury to his right lower extremity that required emergency surgery . Postoperatively, the patient developed a life-threatening, necrotizing, soft-tissue infection and sepsis . Hyperbaric oxygen therapy was used with surgery and antibiotics to control this rapidly progressive infection and to limit the extent of debridement needed . It was found to reverse the patient's deteriorating status and to halt the progression of the necrotizing infection . The scientific evidence for the use of hyperbaric oxygen in such cases is discussed.

Anesthesiology, 1990 Oct, 73(4), 671 - 85
hemofiltration reverses left ventricular dysfunction during sepsis in dogs; Gomez A et al.; Depressed left ventricular (LV) contractility in sepsis has been ascribed to the presence of circulating cardiodepressant substance (filterable cardiodepressant factor in sepsis {FCS}); however, this finding is controversial . The authors hypothesized that if a decrease in LV contractility indeed occurred due to a circulating depressant substance, then removal of this substance by hemofiltration would reverse by dysfunction . In this study, LV mechanics were examined before and after hemofiltration in anesthetized dogs during continuous intravenous infusion of live Escherichia coli . Left ventricular anterior-posterior and apex-base dimensions were measured by subendocardial ultrasonic crystal transducers implanted 4 weeks before the experiments . Left ventricular contractility was determined from the end-systolic pressure-dimension relationship . The slope of this relationship (Emax) is an index of contractility . After 4 h of sepsis, Emax was reduced by one half . Hemofiltration resulted in a return of Emax to control values . The FCS activity in the plasma was also assessed by the percent reduction in isometric contraction of electrically stimulated, isolated right ventricular trabeculae obtained from nonseptic dogs . The FCS activity reached a peak 4 h after sepsis and was reduced after 2 h of hemofiltration . The results show that during experimental sepsis, a circulating substance of less than 30,000 d produces a decrease in LV contractility and that this LV dysfunction may be improved by hemofiltration.

Crit Care Med, 1990 Oct, 18(10), 1055 - 60
Sepsis-related cardiogenic shock; Jardin F et al.; To further define cardiovascular abnormalities in patients with septic shock, serial conventional hemodynamic measurements combined with two-dimensional echocardiographic studies were performed at the bedside in 21 patients admitted for an acute episode of sepsis-related circulatory failure . Measurements obtained during the first hours of hospitalization revealed a group of six patients (group 1) with markedly depressed left ventricular function, as evidenced by a low cardiac index (CI) (2.2 +/- 0.8 L/min.m2), reduced left ventricular ejection fraction (LVEF) (21 +/- 8%), and an increased arterial-venous oxygen content difference . Right ventricular systolic function was also severely depressed . These patients were characterized as having sepsis-related cardiogenic shock secondary to profound myocardial depression, which was reversible within 24 to 48 h with inotropic support . The 15 remaining patients (group 2) exhibited an initially increased CI (4.9 +/- 1.8 L/min.m2), with a low systemic vascular resistance . In group 2, LVEF remained within the normal range despite abnormally low peripheral vascular resistance . This finding would suggest the presence of slight to moderate depression of left ventricular systolic function . All patients in this series had a normal left ventricular end-diastolic volume, whether profound myocardial depression was present or not.

J Pediatr Surg, 1990 Oct, 25(10), 1030 - 3
The hidden mortality in surgically treated necrotizing enterocolitis: fungal sepsis; Smith SD et al.; From 1979 to 1986, 82 infants underwent surgical treatment for necrotizing enterocolitis (NEC), with 36 deaths . The records of 30 of the 36 infants who died were available for review . Fungal colonization and sepsis, the sites of infection, and timing of diagnosis and therapy were determined . Sixteen of 30 (53%) neonates had no evidence of fungus . Six (20%) were colonized with Candida species . Eight (27%) had fungal sepsis, with two of these eight found only at necropsy . Positive fungal blood cultures were a late finding . In only four of the six patients with positive blood cultures were the results known in time to initiate treatment with amphotericin B . Two of these four babies received less than 2 days of amphotericin B treatment prior to death . Fungal sepsis is a significant lethal factor in the surgical mortality of NEC . Vigorous efforts at earlier diagnosis are mandatory.

Arch Surg, 1990 Sep, 125(9), 1132 - 5
Peritoneal lavage in abdominal sepsis . A controlled clinical study; Schein M et al.; The value of intraoperative peritoneal lavage (IOPL) with saline solution, with or without antibiotics, in the treatment of peritoneal contamination, continues to be controversial . A prospective trial was carried out in 87 patients who underwent emergency laparotomies for peritonitis . They were randomized to be treated in one of three ways: group 1 (mean acute physiologic and chronic health evaluation {APACHE} II score, 8) received no IOPL; group 2 (mean APACHE II score, 10) received IOPL with saline solution; and group 3 (mean APACHE II score, 8) received IOPL with saline solution and 2 g of chloramphenicol succinate . In groups 1, 2, and 3, the mortality was 21%, 21%, and 10%, respectively (not significant), and correlated well with the preoperative APACHE II scores . In groups 1, 2, and 3, the mean hospital stay was 13, 13, and 10 days, respectively (not significant), and the incidence of wound infections was 20%, 17%, and 17%, respectively; the incidence of surgical complications was 10%, 24% and 7%, respectively (not significant), and of medical complications, 24%, 31%, and 17%, respectively . We concluded that IOPL with saline solution or antibiotics did not influence the outcome following laparotomies for peritonitis.

Am Surg, 1990 Sep, 56(9), 530 - 2
Physiologic amputation for acute pedal sepsis; Bunt TJ; There are three options for management of pedal sepsis requiring lower extremity amputation: one-stage emergency, two-stage guillotine, or physiologic amputation . The excessive mortality usually ascribed to amputation surgery is basically derived from the selection of one of these options in emergency situations, with published mortalities of 10 per cent to 40 per cent being the norm . We have performed 465 lower-extremity amputations for vascular insufficiency for seven years, with overall 30-day operative mortalities of 0.5 per cent for below-knee amputations and 2.7 per cent for above-knee amputations . One hundred sixteen of these patients presented with acute pedal sepsis superimposed on significant medical disability, and were managed initially with physiologic amputation and intensive hemodynamic monitoring; the overall mortality for this select group was 5.1 per cent . An algorithm of management of patients presenting with acute pedal sepsis has thereby been derived, and is herein presented.

S Afr Med J, 1990 Sep 1, 78(5), 260 - 3
The effect of sepsis and short-term exposure to nitrous oxide on the bone marrow and the metabolism of vitamin B12 and folate; van Achterbergh SM et al.; It is recognised that prolonged anaesthesia with nitrous oxide (N2O) induces megaloblastic anaemia by oxidising vitamin B12 . To determine whether sepsis aggravates the effect of N2O on haemopoiesis 5 patients with severe sepsis, who required surgery and were exposed to short-term (45-105 minutes) N2O anaesthesia, were studied . None had evidence of pre-operative vitamin B12 or folate deficiency . The effect of the combination of N2O anaesthesia and sepsis on DNA synthesis in bone marrow cells was assessed morphologically, and by the deoxyuridine suppression test . In 3 patients exposed to the longest duration (75-105 minutes) of N2O, addition of folinic acid and vitamin B12 partially improved the utilisation of deoxyuridine in vitro . No patient had evidence of megaloblastic haemopoiesis as judged by bone marrow morphology . It is concluded that prolonged N2O anaesthesia in patients with severe sepsis may adversely affect DNA synthesis . Although this effect did not manifest as overt megaloblastic erythropoiesis, it may be prudent to avoid N2O in such patients.

Infection, 1990 Sep-Oct, 18(5), 253 - 62
Cardiovascular parameters and scoring systems in the evaluation of response to therapy in sepsis and septic shock; Pilz G et al.; In 47 medical and postoperative ICU patients with 57 episodes of sepsis and septic shock, cardiovascular parameters including systemic vascular resistance (SVR), cardiac index (CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI) as well as six scoring systems (APACHE II, Elebute, Goris, HIS, SAPS and SSS) were studied regarding their usefulness in the assessment of disease progression and evaluation of response to supplemental sepsis therapy (immunoglobulins, plasmapheresis) . Among the hemodynamic parameters, only a prompt SVR improvement significantly discriminated between ultimate survivors and nonsurvivors . Thus, an increase in SVR (greater than 160 dyn*cm-5*sec, within days 0 to 4, persisting for greater than 24 hours) can serve as a prognostically validated "response" criterion (responders/non-responders: 26/31; mortality: 27% vs . 77%) . Non-invasively, the APACHE II score was best suited (specificity: 88%, sensitivity: 67%) to classify hemodynamically defined responders to supplemental sepsis treatment (score-reduction greater than or equal to 4 on day 4 after onset of therapy).

Acta Chir Scand, 1990 Sep, 156(9), 613 - 20
Early detection of gastrointestinal mucosal ischemia in porcine E . coli sepsis; Montgomery A et al.; The aim of this study was to investigate the oxygenation of the gastrointestinal tract mucosa using indirect pH measurements in a porcine septic model (intravenous infusion of live E . coli) . By means of intraluminally placed balloon catheters (Tonomitior) permeable to CO2, intramucosal pH (pHi) was calculated using the Henderson-Hasselbalch equation . Cardiopulmonary hemodynamics and portal blood flow were measured using Swan-Ganz catheters . Samples were taken from the gastrointestinal tract for histological examination . Nine pigs were given i.v . E . coli infusion while six pigs served as sham controls and were given an equivalent amount of Ringer's solution only . All septic animals developed hemodynamic signs of septic shock . Gastric, small intestinal and sigmoid colonic pHi decreased gradually during the four hour observation period . In the small intestine and the sigmoid colon the decrease was significant already after one hour (p less than 0.01 and p less than 0.02, respectively) . Microscopic examination of tissue specimens obtained 4 hours following induction of sepsis revealed normal or close to normal findings in all the sham and in more than half of the septic animals . These findings indicate that abnormally low gastrointestinal intramucosal pH may be found early in septicemia, preceding microscopically detectable damage by several hours . It is concluded that the tonometer technique does provide early detection of gastrointestinal ischemia in septic shock.

Anaesthesist, 1990 Sep, 39(9), 439 - 44
{Lymphocyte subpopulations in patients at risk of sepsis in a surgical intensive care unit}; Kabisch S et al.; Infection remains a major cause of morbidity and mortality in intensive care medicine . The increased susceptibility of the severely injured patient to sepsis and consecutive multiorgan failure has been attributed to abnormalities in cell-mediated immunity . The purpose of our study was to determine changes in the pattern of lymphocyte subpopulations in severely injured patients and to relate these changes to any development of sepsis and to outcome (indirect immunofluorescence with monoclonal antibodies) . During 14 months we investigated 28 patients (ages 15-65 years) suffering from severe multisystem trauma (22 cases) or diffuse peritonitis (6 cases), 6 of whom (21.4%) developed sepsis and multiorgan failure; 4 of these 6 septic patients died . According to the clinical data, patients developed sepsis between the 3rd and 6th days after trauma . We therefore defined days 1-3 as the preseptic phase, days 3-6 as the phase of sepsis development, and days 4-10 as the phase of septic disease . In the preseptic phase there was no statistically significant difference in the pattern of the eight lymphocyte subpopulations measured between patients who later developed sepsis and those who did not . During the phase of sepsis development, however, the patients who did develop sepsis showed significantly reduced numbers of CD2-, CD8-, and CD20-positive cells (P = 0.0003; P = 0.009; P = 0.012) . The number of helper cells (CD4) was also decreased, but the difference between the two groups failed to reach statistical significance (P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Semin Respir Infect, 1990 Sep, 5(3), 233 - 47
Host responses in mediating sepsis and adult respiratory distress syndrome; Strieter RM et al.; Despite significant advances in intensive care unit technology and mechanical ventilatory support, mortality due to adult respiratory distress syndrome (ARDS) or multiorgan failure (MOF) has not changed significantly within the past two decades . The key to improving survival requires understanding and modifying (or eliminating) factors that may initiate (or modulate) these syndromes . Infection, and the host responses to infection, are major etiological factors responsible for the induction and perpetuation of the injury to the lung and microvasculature in ARDS and MOF, and contribute to late mortality . While the pathogenesis of ARDS and MOF-complicating sepsis remains to be elucidated, bacterially derived (eg, endotoxin or lipopolysaccharides {LPS}) and host-derived humoral and cellular mediators are of importance in both disease states . In fact, the host response to infection (or injurious stimuli) may be a more critical determinant of the outcome of sepsis and ARDS than the original inciting stimulus . The pleiotropic effects of LPS are largely indirect, and are orchestrated via its ability to trigger the release of an array of host-derived mediators of inflammation . Several potential mechanisms of injury in ARDS, sepsis, and MOF have been suggested and include a variety of inflammatory cells (neutrophils, mononuclear phagocytes, platelets), activated complement and coagulation components, vasoactive mediators (kinins, arachidonic acid metabolites, lipids, peptides), reactive oxygen radicals, and diverse cytokines . Interactions between these humoral and cellular mediators appear to set in motion an amplified cascade of events culminating in cellular and tissue injury . In this article, several of these putative inflammatory mediators are discussed in detail, and the importance of cytokine networking and the possible role of nonimmune cells in the orchestration of the inflammatory response associated with ARDS and MOF are explained . Finally, future therapeutic strategies aimed at blocking or suppressing the release or effects of endogenous mediators may be the key to improving the outcome of these disorders.

P N G Med J, 1990 Sep, 33(3), 253 - 6
Anaesthesia and surgery in sepsis; Oberoi GS; Administration of anaesthesia to patients with sepsis and its effects on the progression of infection in the postoperative period is an important consideration both for surgeons and anaesthetists . All cases of abdominal sepsis carry a surgical mortality of around 50% . Though appropriate therapy is virtually always surgical, limiting initial surgical stress to simple closure and irrigation, supplemented with a proper anaesthetic regime, nutritional care and antibiotic cover, can improve the outcome.

J Clin Invest, 1990 Aug, 86(2), 474 - 80
Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome; Rubin DB et al.; In this prospective study of 45 patients, we tested the hypothesis that markedly elevated levels of plasma von Willebrand antigen (vWf-Ag) a marker of endothelial cell injury, might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome . Acute lung injury was quantified on a four-point scoring system . At the time of entry into the study, none of the 45 patients had evidence of lung injury . Subsequently, 15 patients developed lung injury and 30 patients did not develop lung injury . The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury (588 +/- 204 vs . 338 +/- 196, percentage of control, P less than 0.01) . Furthermore, a plasma vWf-Ag level greater than or equal to 450 was 87% sensitive and 77% specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis . In addition, the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80% for acute lung injury . Also, a plasma vWf-Ag level greater than 450 had a positive predictive value of 80% for identifying nonsurvivors . Thus, in patients with nonpulmonary sepsis, an elevated level of plasma vWf-Ag is a useful, early biochemical marker of endothelial injury and it has both predictive and prognostic value.

Surgery, 1990 Aug, 108(2), 460 - 6
Interaction between corticosterone and tumor necrosis factor stimulated protein breakdown in rat skeletal muscle, similar to sepsis; Hall-Angeras M et al.; Protein synthesis and breakdown rates were determined in incubated extensor digitorum longus muscles of rats treated with tumor necrosis factor (TNF; 20 micrograms/100 gm body weight), corticosterone (20 mg/100 gm body weight), or a combination of the two substances . Protein synthesis was measured as incorporation of carbon 14-labeled phenylalanine into protein . Total and myofibrillar protein breakdown rates were assessed as release of tyrosine and 3-methylhistidine, respectively . Administration of TNF alone did not affect muscle protein turnover rates . Corticosterone inhibited muscle protein synthesis and stimulated total and myofibrillar protein breakdown . When TNF was administered together with corticosterone, total and myofibrillar protein breakdown rates were increased further compared with rats treated with corticosterone alone . Because plasma corticosterone levels in rats treated with both TNF and the glucocorticoid were higher than in animals treated with corticosterone alone, it is possible that muscle proteolysis noted after TNF, injected together with costicosterone, was caused by the high glucocorticoid levels . To test that hypothesis, corticosterone alone or in combination with TNF was injected in rats that had undergone adrenalectomy . In these experiments, TNF did not increase plasma corticosterone levels or muscle protein breakdown rates . The results suggest that muscle catabolism induced by administration of TNF is mediated by glucocorticoids.

Crit Care Med, 1990 Aug, 18(8), 851 - 7
Pharmacodynamic response to ionized calcium during acute sepsis; Steinhorn DM et al.; Ionized Ca (Ca2+) is essential for maintaining physiologic functioning in the cardiovascular system (CVS) . Sepsis affects the CVS by several mechanisms and is associated with decreased serum Ca2+ . The pharmacodynamic response of the CVS to serum Ca2+ alteration was compared in acutely septic and nonseptic dogs at serum Ca2+ levels of 50%, 100%, 150% and 200% of normal baseline values . Serum Ca2+ alterations caused similar changes in both groups, although finite differences existed between septic and nonseptic subjects . Ca manipulation produced limited differences in the response of mean arterial pressure, cardiac output, left ventricular dP/dtmax, systemic (SVR) and pulmonary (PVR) vascular resistance between septic and nonseptic subjects . PVR and SVR demonstrated opposite responses during hypocalcemia; PVR was lower than baseline in both groups, whereas SVR was higher at the 50% level . No difference was evident for total oxygen consumption (VO2) or heart rate . In view of the limited differences in response and the failure to improve systemic VO2, serum Ca2+ supplementation does not afford any additional benefit in this experimental model of acute sepsis.

J Trauma, 1990 Aug, 30(8), 1027 - 31
Untreated intra-abdominal sepsis: lack of synergism between polymorphonuclear leukocyte (PMN) complement receptors CR1/CR3 and IgG receptor FcRIII; Simms HH et al.; We have examined the effects of untreated intra-abdominal sepsis on polymorphonuclear leukocyte (PMN) phagocytosis . Phagocytosis was studied in a receptor-specific fashion looking at the interrelationship between FcRIII-, complement receptor (CR1)-, and complement receptor 3 (CR3)-mediated phagocytosis . Twelve swine underwent either sham laparotomy (n = 5) or laparotomy with cecal ligation and incision (n = 7) to induce intra-abdominal sepsis . PMN phagocytosis was assayed on POD 1, 4, and 8 . In animals undergoing sham laparotomy, FcRIII-mediated phagocytosis was less than 10% on all days and was augmented with the addition of C3b or C3bi to the target particles (FcR + CR1 or FcR + CR3 greater than FcR alone) . In animals undergoing cecal ligation and incision, baseline FcRIII-mediated phagocytosis increased between POD 1 and 4 and fell between POD 4 and 8 . No increase in phagocytosis was seen on POD 4 or 8 with the addition of C3b or C3bi to the target particles (FcR + CR1 or FcR + CR3 = FcR alone) . Preligation of the FcRIII but not FcRII or FcRI receptor with a monoclonal antibody (3G8) markedly reduced phagocytosis in the animals with intraabdominal sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Surg, 1990 Aug, 77(8), 924 - 9
Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial; von Meyenfeldt MF et al.; Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients . Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown . We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality . One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution . Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight . In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA) . Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA) . Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups . Although morbidity scores tended to decrease during the study no difference was observed between groups . Mortality (early or late), sepsis or stress-related, did not differ significantly between groups . We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.

Crit Care Med, 1990 Jul, 18(7), 709 - 14
Left ventricular diastolic function in sepsis; Jafri SM et al.; Although systolic dysfunction of the left ventricle has been characterized in septic shock (SS) and sepsis without shock (SWS), diastolic abnormalities are less well characterized . Diastolic filling was determined using pulsed Doppler transmitral spectral tracings in 13 patients with SS, ten patients with SWS, and 33 normal controls . Diastolic filling variables and heart rate were similar in patients with SS and SWS . The SS and SWS patients had an abnormal pattern of diastolic filling compared with controls and were characterized by an increase in peak atrial velocity (70 +/- 20 cm/sec SS, 84 +/- 18 cm/sec SWS vs . 56 +/- 11 cm/sec controls, p less than .05), decreased peak rapid filling velocity/peak atrial filling velocity (1.1 +/- 0.3, SS, 1.1 +/- 0.2 SWS vs . 1.5 +/- 0.4 controls, p less than .05), increased atrial filling fraction (39 +/- 11 SS, 42 +/- 6 SWS vs . 30 +/- 10 controls, p less than .05) and prolongation of atrial filling period as a function of the diastolic filling period (0.48 +/- 0.10 SS, 0.43 +/- 0.10 SWS vs . 0.30 +/- 0.07 controls, p less than .05) . Heart rate was higher in SS and SWS compared with controls (116 +/- 15 beat/min SS, 110 +/- 26 beat/min SWS vs . 73 +/- 12 beat/min controls, p less than .05) . In patients with SS and SWS, there is increased reliance on atrial systolic contribution to diastolic filling . We conclude that diastolic dysfunction occurs with systemic infections.

J Surg Res, 1990 Jul, 49(1), 49 - 54
Intraabdominal sepsis: effects on polymorphonuclear leukocyte Fc receptor-mediated phagocytosis; Simms HH et al.; In vitro studies have shown that phagocytic cells are capable of undergoing activation in response to inflammatory signals and that the activation process is quite complex . A relationship between polymorphonuclear leukocyte (PMN) Fc receptor-mediated phagocytosis and oxidative metabolism has been seen in humans . We have sequentially examined circulating polymorphonuclear leukocytes (PMNs) from a total of 13 postoperative swine with either no sepsis, untreated intraabdominal sepsis, or treated intraabdominal sepsis to determine phagocytic activity over 8 postoperative days (POD) . Products of the oxidative burst (i.e., myeloperoxidase) reduced the phagocytic activity of nonseptic swine PMN . Phagocytic activity was augmented by inhibiting the nonseptic swine oxidative burst with 10 mM sodium azide (an inhibitor of myeloperoxidase) . In swine with untreated intraabdominal sepsis, PMN Fc receptor-mediated phagocytosis exhibited a biphasic response . An initial (between POD1 and POD4) increase in PMN function was followed by a subsequent (between POD4 and POD8) decrease in PMN function . Partial preservation of phagocytic capability was seen when swine were reexplored on POD4 and had their intraabdominal sepsis treated . These results indicate that (1) as in humans, nonseptic swine PMN Fc receptor-mediated phagocytosis is augmented by inhibition of the PMN respiratory burst; (2) untreated intraabdominal sepsis produces an initial increase and subsequent decrease in PMN Fc receptor-mediated phagocytosis; (3) early treatment of intraabdominal sepsis results in partial restoration of PMN Fc receptor-mediated phagocytosis.

Mikrobiyol Bul, 1990 Jul, 24(3), 205 - 13
{IgG therapy of experimental E . coli sepsis in neutropenic mice}; Dokmetas I et al.; The treatment of Ceftriaxone and IgG in neutropenic (Group A), and in normal (Group B) mice were investigated in experimental E . coli sepsis . IgG was obtained from the rabbits immunized with same strain . The inoculum dose of infection was 4 x 10(8) bacteria/ml in the experiment . The two groups were divided into four subgroups; Control, IgG . Ceftriaxone and Ceftriaxone + IgG groups . The mortality rates of mice in both groups and bacteria growing in organ cultures are investigated and compared . IgG treatment reduced the mortality in the normal mice, but no significant difference was found between two groups . An addition of IgG to Ceftriaxone treatment significantly decreased the mortality rate in both of the groups (p less than 0.05) . But a significant difference was not observed between two subgroups treated with IgG and Ceftriaxone.

Clin Podiatr Med Surg, 1990 Jul, 7(3), 545 - 63
Ankle arthrodesis in the presence of continuous sepsis . Indications, methods, and results; Cierny G 3rd et al.; On 26 patients, 28 ankle fusions were performed and followed 2 or more years . A functional limb salvage was gained in 25 limbs (96%) with an overall arrest rate of 92% . There was one amputation (4%) . The major complication rate was 38% for the series and 86% for patients with uncorrected wound-healing deficiencies (B-hosts) . All of the first and second treatment failures were associated with a central column deficiency (C-).

Ophthalmology, 1990 Jul, 97(7), 882 - 8
Bilateral ischemic optic neuropathy and retinal vascular occlusions associated with lymphoma and sepsis . Clinicopathologic correlation; Guyer DR et al.; The authors report the clinicopathologic correlation of a patient with non-Hodgkin's mixed-cell lymphoma who had impairment of the circulation of the optic nerve and retina in both eyes . The results of histopathologic examination showed that the pial septa of the optic nerves were infiltrated by lymphoma and that there was extensive infarction of the orbital portions of both optic nerves and occlusion of both central retinal arteries and the right central retinal vein by thrombi with bacteria . The infiltration of the optic nerves seemed to be resistant to therapy.

Circ Shock, 1990 Jul, 31(3), 351 - 63
Glucoregulatory, hormonal, and metabolic responses to endotoxicosis or cecal ligation and puncture sepsis in the rat: a direct comparison; Yelich MR; This study characterized the cecal ligation and puncture (CLP) model of sepsis and the bolus endotoxin model of sepsis in rats with regard to specific hormonal, metabolic, and glucoregulatory changes which occur during the early, compensatory phases of sepsis . Plasma levels of glucose, lactate, insulin, and glucagon were measured during the initial 5 hr of endotoxicosis and CLP sepsis . During this time period, endotoxic and CLP septic rats displayed similar metabolic changes, particularly hyperglycemia, hyperlactacidemia, hyperinsulinemia, and hyperglucagonemia relative to their respective control groups . The metabolic and hormonal similarities observed between these two models of sepsis are consistent with the concept that endotoxin plays a role as a mediator of human and animal sepsis.

J Pediatr Surg, 1990 Jun, 25(6), 599 - 603
Fluid and ion redistribution in skeletal muscle in an animal sepsis model; Hannon RJ et al.; The redistribution of fluid and electrolytes was investigated in a hyperdynamic sepsis animal model using cecal ligation and puncture (CLP) in Wistar rats . Hyponatremia was not observed . There was a significant shift of sodium, chloride, and water from the extracellular into the intracellular space as early as 12 hours following CLP . These data suggest that the mechanism by which hyponatremia occurs in clinical sepsis is not caused by shift of fluid from the intracellular to the extracellular space as proposed by the sick cell theory . This is more likely to result from fluid retention and dilution of the extracellular space possibly on the basis of antidiuretic hormone secretion.

Ann Surg, 1990 Jun, 211(6), 708 - 16; discussion 716-8
Long peritoneal lavage decreases pancreatic sepsis in acute pancreatitis; Ranson JH et al.; Late infection of devitalized pancreatic and peripancreatic tissue has become the major cause of morbidity in severe acute pancreatitis . Previous experience found that peritoneal lavage for periods of 48 to 96 hours may reduce early systemic complications but did not decrease late pancreatic sepsis . A fortunate observation led to the present study of the influence of a longer period of lavage on late sepsis . Twenty-nine patients receiving primary nonoperative treatment for severe acute pancreatitis (three or more positive prognostic signs) were randomly assigned to short peritoneal lavage (SPL) for 2 days (15 patients) or to long peritoneal lavage (LPL) for 7 days (14 patients) . Positive prognostic signs averaged 5 in both groups but the frequency of five or more signs was higher in LPL (71%) than in SPL (47%) . Eleven patients in each group had early computed tomographic (CT) scans . Peripancreatic fluid collections were shown more commonly in LPL (82%) than in SPL (54%) patients . Longer lavage dramatically reduced the frequency of both pancreatic sepsis (22% LPL versus 40% SPL) and death from sepsis (0% LPL versus 20% SPL) . Among patients with fluid collections on early CT scan, LPL led to a more marked reduction in both pancreatic sepsis (33% LPL versus 83% SPL) and death from sepsis (0% LPL versus 33% SPL) . The differences were even more striking among 17 patients with five or more positive prognostic signs . In this group the incidence of pancreatic sepsis was 30% LPL versus 57% SPL and of death from sepsis 0% (LPL) versus 43% (SPL) (p = 0.05) . In these patients, overall mortality was also reduced (20% LPL versus 43% SPL) . When 20 patients treated by LPL were compared with 91 other patients with three or more positive prognostic signs who were treated without lavage or by lavage for periods of 2 to 4 days, the frequency of death from pancreatic sepsis was reduced from 13% to 5% . In those with five or more signs, the incidence of sepsis was reduced from 40% to 27% (p = 0.03) and of death for sepsis from 30% to 7% (p = 0.08) . These findings indicate that lavage of the peritoneal cavity for 7 days may significantly reduce both the frequency and mortality rate of pancreatic sepsis in severe acute pancreatitis.

P N G Med J, 1990 Jun, 33(2), 155 - 7
Fatal post-splenectomy sepsis in a Papua New Guinean highlander; Sapuri M et al.; A fatal case of overwhelming post-splenectomy sepsis (OPSS) occurring 5 years after splenectomy for trauma in a Papua New Guinean highlander is presented . The diagnosis of pneumococcal infection was made from a peripheral blood smear . The finding of OPSS in Papua New Guinea is cited as additional evidence in favour of a policy of conservative management, where possible, of ruptured spleen.

Crit Care Nurs Clin North Am, 1990 Jun, 2(2), 151 - 60
Cellular and humoral mediators of sepsis syndrome; Stroud M et al.; The story of mediators in sepsis syndrome is developing extremely rapidly and continues to unfold . This discussion has focused on those areas most studied and those that have the greatest clinical implications in the context of current knowledge . There are a number of mediators under active investigation that have not been reviewed here because their discussion is beyond the scope of this article . Just how all the pieces of the intricate cascade of events ultimately fit together is yet to be seen . However, the availability of important probes, such as cyclooxygenase inhibitors, TNF, anti-TNF, IL1, anti-IL1, anti-proteases, antioxidants, and antiendotoxin, is allowing major progress to be made in a short period of time . Transferring this knowledge to the bedside and everyday clinical practice is a slower process, but the prospects are bright for innovative new therapies for sepsis syndrome, septic shock, and the multiple organ failure associated with these clinical entities.

Aust N Z J Surg, 1990 Jun, 60(6), 467 - 70
Sequential laparotomy and zipper closure in the management of gross peripancreatic sepsis; Hughes CJ et al.; Four cases of gross peripancreatic sepsis have been managed with repeated laparotomies and packing of the lesser sac . A zipper was used for abdominal closure in three patients and the abdomen was left open in one . Sequential laparotomy enabled repeated debridement of non-viable pancreatic and peripancreatic tissue and prevented intra-abdominal septic accumulations . An additional benefit of this technique was the frequent detection and correction of clinically unsuspected complications of the septic abdomen.

J Pharmacol Exp Ther, 1990 Jun, 253(3), 1171 - 6
Bacterial sepsis-induced decrease in lung vascular reactivity to 9,11-dideoxy-11a9a-epoxymethano-prostaglandin F2 alpha (U46619) in the rat; Schneidkraut MJ et al.; This study determined whether a sepsis-associated increase in cyclooxygenase products altered the pulmonary vascular response to the thromboxane A2 mimic, 9,11-dideoxy-11a,9a-epoxymethano-prostaglandin F2 alpha (U46619) . Rats were anesthetized (50 mg/kg of sodium pentobarbital i.p.), and sepsis was induced by cecal ligation and puncture . Four hours later, pulmonary effluent immunoreactive thromboxane (iTXB2) levels were significantly increased (156.8%) and pulmonary vascular reactivity to U46619 (50-200 ng) was significantly (P less than .05) decreased compared to lungs from nonseptic controls . This decreased vascular reactivity was not seen in lungs from cecally ligated rats challenged with angiotensin II (5-200 ng) . Sham surgery did not alter pulmonary iTXB2 synthesis nor did it result in a depressed vascular response to U46619 . Rats pretreated with ibuprofen (15 mg/kg i.v.) did not show the sepsis-associated increase in iTXB2 levels nor was a decrease in pulmonary vascular reactivity to U46619 observed . These data indicate that a sepsis-associated increase in TXA2 and/or other cyclooxygenase products can alter the pulmonary vascular response to the TXA2 mimic, U46619.

Crit Care Med, 1990 Jun, 18(6), 585 - 9
Venous hypercarbia associated with severe sepsis and systemic hypoperfusion; Mecher CE et al.; We studied 37 patients with severe sepsis and systemic hypoperfusion to assess changes in PvCO2 . Before fluid administration, the cardiac index (CI) was 2.64 +/- 0.14 L/min.m2 . The PvCO2 was 38 +/- 1 torr and mixed venous pH was 7.32 +/- 0.02 . The venous-arterial CO2 tension gradient (P{v-a}CO2) was 6 +/- 1 torr . After fluid administration, the CI increased to 3.45 +/- 0.14 L/min.m2 (p less than .001) and the P(v-a)CO2 decreased to 5 +/- 1 torr . The correlation between the change in CI and the change in P(v-a)CO2 was r = .42, p less than .01 . P(v-a)CO2 was elevated in 19 (51%) patients before fluid administration (P{v-a}CO2 greater than 6 torr) (hypercarbic group) . The P(v-a)CO2 gradient in this group was 9 +/- 1 compared with 4 +/- 1 torr in 18 patients with a normal P(v-a)CO2 gradient (p less than .001) (normocarbic group) . PvCO2 was 41 +/- 2 torr in the hypercarbic group compared with 35 +/- 2 torr in the normocarbic group (p less than .05) . No difference was noted in PaCO2 . Venous arterial pH and HCO3- gradients were of greater magnitude in the hypercarbic group, -0.05 +/- 0.003 and 2.4 +/- 0.3 mEq/L compared to -0.02 +/- 0.004 (p less than .001) and 1.1 +/- 0.2 mEq/L (p less than .001), respectively . CI in the hypercarbic group was 2.3 +/- 0.2 compared to 3.0 +/- 0.2 L/min.m2 in the normocarbic group (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

JPEN J Parenter Enteral Nutr, 1990 May-Jun, 14(3), 287 - 9
Effect of sepsis and surgery on trace minerals; Shanbhogue LK et al.; The purpose of this study was to evaluate effect of infection and surgery on serum iron, zinc, and the copper simultaneously . Twenty patients who had emergency abdominal surgery for acute inflammatory conditions, and 15 controls who had elective abdominal surgery were studied . Preoperatively, serum iron levels were significantly decreased in the septic group compared to controls (p less than 0.001) . Following surgery and removal of the septic focus, serum iron, ferritin, and zinc levels increased, while serum transferrin levels decreased significantly . Serum copper levels did not show any significant difference . It is concluded that serum iron, transferrin, ferritin, and zinc levels are affected profoundly by septic and the surgical stress.

Arch Surg, 1990 May, 125(5), 651 - 4
Neutrophil activation in acute renal failure and sepsis; Horl WH et al.; Neutrophils are activated during sepsis . To find out whether granulocytes are further activated during hemodialysis with cellulosic and noncellulosic membranes, we compared the plasma levels of the main granulocyte components in patients with chronic uremia who were undergoing regular hemodialysis treatment and patients with acute renal failure with and without sepsis . During hemodialysis with cuprophane dialyzers, plasma-granulocyte elastase, in complex with alpha-proteinase inhibitor, and lactoferrin levels increased in patients who were undergoing regular hemodialysis treatment, but these levels increased further in patients with acute renal failure who did not have sepsis . Maximal neutrophil degranulation was observed in patients with acute renal failure and sepsis . There was only mild degranulation in all three groups during dialysis with dialyzers made of polysulfone . Our data demonstrate that neutrophil activation is increased in patients with acute renal failure, and it is increased further by superimposed sepsis . Cellulose-containing dialysis membranes introduce a further activation of neutrophils.

Crit Care Med, 1990 May, 18(5), 474 - 9
Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unit; Tran DD et al.; We retrospectively studied relations between age, pre-existing chronic disease, sepsis, organ system failure, and mortality in 487 patients from a medical ICU . Single organ system failure (SOSF) occurred in 136 (28%) and multiple (greater than or equal to 2) organ system failure (MOSF) in 187 (38%) patients . Cardiovascular and pulmonary failure predominated . Overall mortality was 27% . SOSF mortality was 16% and for MOSF 58% . Eighty-three percent of nonsurvivors had MOSF . Hence, MOSF is common and a major cause of death in critically ill medical patients . Advancing age and prior chronic disease may diminish physiologic reserve and predispose to sepsis and MOSF . Although sepsis is a major risk factor for MOSF, a nonspecific host response to critical illness may contribute to the syndrome in 35% of patients . Advancing age, chronic disease, and the number of failing organs, particularly failure of cardiovascular, pulmonary, renal, and neurologic systems, are major determinants of overall mortality, but sepsis is not an independent contributor.

Am Rev Respir Dis, 1990 May, 141(5 Pt 1), 1198 - 208
Hyperdynamic sepsis modifies a PEEP-mediated redistribution in organ blood flows; Bersten AD et al.; Changes in organ blood flow (Q) produced by 20 cm H2O positive end-expiratory pressure (PEEP) were measured before and after the induction of hyperdynamic sepsis in nine unanesthetized sheep . During the baseline nonseptic study, PEEP was associated with a 9% fall in thermodilution-measured systemic Q, although arterial perfusing pressures were unaffected . Concurrently, microsphere-derived Q was maintained to the brain and heart, but fell to liver, spleen, pancreas, kidney, large intestine, and gastrocnemius . Twenty-four to 36 h after cecal ligation and perforation, a pre-PEEP septic study demonstrated an increase in all of the cardiac index (CI) (+43%) and systemic O2 delivery (+54%) when compared with the nonseptic study, whereas whole-body O2 extraction (-30%) was depressed . Although PEEP depressed systemic Q (-17%) during the septic study to a greater extent than during the nonseptic study (p less than 0.02), absolute organ Q fell only to pancreas, liver, and spleen . Relative to the simultaneous fall in the CI, Q to some splanchnic organs was not depressed by PEEP to the same magnitude in the septic as in the nonseptic study . When an infusion of Ringer's lactate (993 +/- 295 ml) subsequently restored systemic Q to pre-PEEP septic levels, individual flows that had been depressed by PEEP were not restored . Furthermore, Q-kidney continued to fall, such that the postfluid Q-kidney (-19%) was significantly less than was demonstrated in the pre-PEEP septic study . We postulate that differences noted in the distribution of organ Q between the nonseptic and hyperdynamic septic studies after the application of PEEP were secondary to the vasculopathy of sepsis and/or an alteration in the function of specific organ microcirculations . However, these data do not address whether the changes in organ Q distribution after a PEEP-mediated depression in systemic Q during sepsis significantly restricted tissue DO2 . The inability to acutely reverse the PEEP-mediated changes in organ Q after restoring systemic Q by a fluid infusion also suggests the need to evaluate alternative methods of support to organ Q in acute respiratory failure secondary to sepsis when the addition of PEEP acutely depresses systemic DO2.

Nutr Hosp, 1990 May-Jun, 5(3), 172 - 4
{Catheter sepsis: pathogeny and prevention with a new connection model}; Segura M et al.; A revision is made of the issue regarding sepsis related to central intravenous catheterization . A special point was made on the relevance of latest discoveries in the field of pathogenicity in order to prevent, diagnose and treat this entity . Preventive measures should be geared to avoid intralumen infection, and success may depend on new connection models and industrial preparation of nutrient mixtures . Infected catheters must be removed, but in highly selected patients local and systemic antibiotic therapy may be attempted.

Med J Aust, 1990 Apr 2, 152(7), 352 - 7
111In-oxine labelled leukocyte scintigraphy in the detection and localization of active inflammation and sepsis; Kelly MJ et al.; We report an analysis of the results obtained in our first 100 studies with indium-111-oxine labelled leukocyte scintigraphy, a diagnostic technique which has recently become available for clinical evaluation within Australia . We used this technique to assess patients with suspected sepsis or inflammation after other commonly used investigations had failed to confirm a diagnosis . Four patient subgroups were evaluated: fever of unknown origin; suspected abdominal or postoperative sepsis; suspected active inflammatory bowel disease; and suspected sepsis or inflammation of bones or joints . The course of all patients was followed for at least three months to establish the accuracy of the technique . The leukocyte labelling procedure took 90 min and imaging was carried out typically 3-6, 24 and occasionally 48 h after reinjection of the labelled autologous leukocytes . In one patient labelling of leukocytes was unsuccessful . In the remaining 99 studies the overall sensitivity of leukocyte scintigraphy was 88% (36 of 41 patients with a proved inflammatory or infective disease focus had positive scan findings); and the specificity was 95% (55 of 58 cases with no proved disease focus had normal scan findings) . This series supports the use of this method as the imaging procedure of choice in nuclear medicine for the evaluation of suspected acute sepsis (symptoms less than four weeks' duration), of inflammatory bowel disease and of suspected infections involving appendicular bones which contain no active bone marrow . It is also a useful secondary scintigraphic procedure, after gallium-67-citrate scintigraphy, in patients with suspected infective disorders of more than four weeks' duration.

Ulster Med J, 1990 Apr, 59(1), 36 - 40
Wound sepsis in 10,000 surgical patients; Kirk SJ et al.; A twelve year prospective wound audit was undertaken in an academic surgical unit . Data from 10,000 operations were analysed . Overall, wound infection rates decreased during this time . Infection rates in contaminated wounds in particular fell from 19.2% to 4.7% . This decrease in wound infection may be related in part to a change in the antibiotic prophylactic regimen and in part to the institution of the wound sepsis audit which provided regular information on the unit infection rates . This audit permitted early detection of adverse trends, and may have had a direct influence on surgical techniques.

Br J Surg, 1990 Apr, 77(4), 401 - 4
Effect of low dose recombinant interleukin 2 plus indomethacin on mortality after sepsis in a murine burn model; Horgan PG et al.; Under anaesthesia, 129 8-week-old male A/J mice were subjected to a 25 per cent scald or sham burn and then resuscitated . They were divided at random into two groups . Mice from the first group were allocated into two groups . Mice from the first group were allocated into four subgroups to receive 6 days intraperitoneal (I.P.) injections as follows: (i) recombinant human interleukin 2 (rhIL-2) (250 units day-1); (ii) saline; (iii) indomethacin (5 micrograms-1 day-1); or (iv) rhIL-2 (250 units) + indomethacin (5 micrograms) . Sham burned mice served as no treatment controls . All animals were subjected to peritonitis induced by caecal ligation and puncture 10 days after the burn and mortality was assessed . Mice from the second group were allocated to two subgroups to receive 6 days intraperitoneal injections of: (i) rhIL-2 + indomethacin; or (ii) saline . Animals in this group did not undergo septic challenge . They were randomly killed on days 7, 9 or 10 after the burn . Their splenocytes were harvested and assayed for response to the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A), and for production of interleukin 2 . Mortality rate in animals subjected to burn and septic challenge without treatment was 75 per cent; in mice receiving rhIL-2 alone it was 68 per cent, in mice receiving indomethacin alone it was 62 per cent (no significance) and in mice receiving rhIL-2 + indomethacin it was reduced to 38 per cent (P less than 0.02) . Splenocytes from animals receiving combination therapy had markedly improved responses to PHA on days 7 (P = 0.01), 9 (P = 0.02), and 10 (P = 0.008), and to Con A on days 7 (P = 0.001), 9 (P = 0.002) and 10 (P = 0.001), after burn injury . Interleukin 2 production was also significantly (P = 0.004) improved by therapy with rhIL-2 + indomethacin . These data suggest that low dose rhIL-2 in combination with indomethacin may have potential use in the therapy of burn victims.

J Pediatr Surg, 1990 Apr, 25(4), 422 - 5
Hyponatraemia and intracellular water in sepsis: an experimental comparison of the effect of fluid replacement with either 0.9% saline or 5% dextrose; Hannon RJ et al.; Hyponatraemia associated with sepsis is known to have an increased morbidity and mortality . The cause of this phenomenon is unknown, but may be related to dilution of the extracellular space with retained exogenous fluid . Fluid and ion redistribution across the cell membrane of striated muscle was investigated in an animal sepsis model and compared with sham controls . The objective was to study the effect of different volumes of fluid replacement with either 0.9% saline or 5% dextrose . Significant shifts of sodium, chloride, and water occurred into the cell in all septic animals but not in controls . This trend was exacerbated by the use of dextrose for intravenous replacement even when the estimated normal fluid requirements had not been exceeded . Hyponatraemia and plasma hypoosmolality were induced only in septic animals, which received 100% of their fluid requirements as dextrose . These animals at the same time had significantly reduced extracellular and increased intracellular volumes compared with controls and the septic animals that received saline replacement . It is concluded that the hyponatraemia and plasma hypoosmolality that occurs in these animals is caused by a combination of intracellular shift of sodium and water, and dilution of the extracellular space, probably on the basis of physiological antidiuretic hormone (ADH) secretion . Dextrose (and by implication 4% dextrose/0.18% saline) is inappropriate, potentially dangerous, and should be avoided in these circumstances.

Arch Surg, 1990 Apr, 125(4), 510 - 4
Is there a circulating proteolysis-inducing factor during sepsis?
Hasselgren PO, James JH, Benson DW, Li S, Fischer JE.
Muscles from fed or 72-hour fasted rats were incubated in the presence of plasma from septic rats, recombinant interleukin 1 alpha (rIL-1 alpha), or recombinant tumor necrosis factor alpha (rTNF alpha), and breakdown of total and myofibrillar protein was assessed by determining release of tyrosine and 3-methylhistidine, respectively . Septic plasma stimulated total protein breakdown in muscles from 72-hour fasted rats by 10% to 20%, while myofibrillar protein breakdown was not affected . When septic plasma was added to muscles from fed rats, neither tyrosine nor 3-methylhistidine release was altered . Various concentrations of recombinant interleukin 1 alpha or recombinant tumor necrosis factor alpha did not affect total or myofibrillar protein breakdown . Since septic plasma did not stimulate myofibrillar protein breakdown, the role of a circulating factor for muscle proteolysis during sepsis remains unclear.

Arch Surg, 1990 Apr, 125(4), 441 - 3
Hepatic parenchymal oxygen tension following injury and sepsis; Dahn MS et al.; Hepatic blood flow and splanchnic oxygen consumption were measured in 16 injured (n = 6) or septic (n = 10) patients and compared with values in 16 normal volunteers . Sepsis and injury appeared to stimulate an increase in blood flow and oxygen utilization, with the highest levels observed in the septic group . Patients with sepsis exhibited a 72% and 60% increase in hepatic blood flow and splanchnic oxygen consumption, respectively, compared with normal volunteers . Application of these data to the Krogh-Erlang tissue model indicates that despite an increase in oxygen delivery to the splanchnic bed during sepsis, it becomes more sensitive to hypoxic/ischemic events compared with other patient groups . This is indicated by a reduced centrilobular and increased critical oxygen tension . The major factor responsible for this is the regional hypermetabolism present in sepsis . This analysis emphasizes the critical importance of maintaining oxygen transport in critically ill patients with sepsis.

Surgery, 1990 Apr, 107(4), 397 - 410
Histologic and ultrastructural changes in nonpulmonary organs during early hyperdynamic sepsis; Hersch M et al.; Previous studies describing the histologic elements of multi-system organ failure caused by bacterial sepsis may have been complicated by a significant interaction on tissue injury from either a preterminal low-flow state or the effects of therapy immediately before death . Therefore we evaluated the nonpulmonary histologic findings of sepsis during a 3-day period that followed cecal ligation and perforation . In this septic model, mean arterial perfusion pressures remained unchanged from baseline, systemic flows rose by 54%, and laboratory evidence of organ dysfunction including an elevation of the serum bilirubin levels and a depression of the serum total protein values was considered mild . Concurrently, development of the hyperdynamic central circulatory septic state was associated with widespread histologic changes in myocardium, striated muscle, liver, gut, and pancreas . Lesions common to these organs included high-protein interstitial and intracellular edema, mitochondrial destruction, and patchy cell necrosis . Lesions within the pancreas were exaggerated over those noted in other organs . Of all organs examined, only the liver demonstrated microvascular neutrophil accumulation . Unlike models of shock caused by sepsis, fibrin thrombi were not seen in the microvasculature of any organ . We conclude that tissue injury characterized by the accumulation of protein-rich extravascular fluid and the development of reversible and irreversible cell injury antedated significant multiple-system organ failure in this animal model of normotensive sepsis.

Circ Shock, 1990 Apr, 30(4), 331 - 47
Sequential changes in lipid metabolism and the fatty acid profile in liver lipids during fasting and sepsis; Larsson-Backstrom C et al.; The sequential changes in lipid metabolism and in the fatty acid profile of liver lipids during fasting and sepsis were studied . Liver and blood specimens were taken from normally fed rats and from nonseptically and septically fasted rats at 5, 24, and 48 hr . Sepsis was induced by injecting live Escherichia coli bacteria intraperitoneally . Sepsis attenuated the fasting-induced increase in beta-hydroxybutyrate and reduced liver and serum triglycerides at 5 hr . There was a percentage decline in the most abundant fatty acids in neutral lipids, namely oleic (18:1w9) and linoleic (18:2w6) acids . This was seen throughout fasting and septic fasting . These results indicate that 18:1w9 and 18:2w6 are used as energy substrates and are oxidized to beta-hydroxybutyrate during fasting and mainly to carbon dioxide during septic fasting . On the contrary, the most abundant fatty acids in phospholipids, stearic (18:0), arachidonic (20:4w6), and docosahexaenoic (22:6w3) acids, accumulated in neutral lipids and in phospholipids throughout fasting . However, during sepsis this accumulation was reduced in neutral lipids and reversed to a level below that in the fed and fasted state in phospholipids . These results indicate that a disturbance in membrane integrity and function induced by septic fasting may have pathophysiological consequences for lipid metabolism and liver function during sepsis.

Metabolism, 1990 Apr, 39(4), 335 - 40
Effect of sepsis on amino acid transport system A and its response to insulin in incubated rat skeletal muscle; James JH et al.; The effect of sepsis on neutral amino acid transport systems A, ASC, and L, was studied in incubated rat soleus (SOL) muscles . We also examined the effects of plasma from septic rats and of varying concentrations of insulin (10 to 10(5) microU/mL), added in vitro to incubated muscles, on system A amino acid transport . Sepsis was induced by cecal ligation and puncture (CLP) in rats weighing 40 to 60 g . Control rats were sham-operated . System A activity was assessed by determining uptake of 2-(methylamino)isobutyrate (MeAIB) 16 hours after CLP or sham-operation . System ASC was studied by measuring uptake of alpha-aminoisobutyric acid (AIB) in the presence of 25 mmol/L MeAIB and 25 mmol/L 2-amino-2-norbornane carboxylic acid (BCH) to inhibit uptake by systems A and L . System L activity was defined as sodium-independent uptake of cycloleucine . MeAIB uptake was reduced by 28% in muscles of septic rats, while amino acid transport by systems ASC and L was almost identical in muscles from control and septic rats . Addition of plasma from septic rats to incubated normal SOL muscles inhibited MeAIB uptake by 31% . Addition of insulin to the incubation medium resulted in increased uptake of MeAIB, both in nonseptic and septic muscle . The lowest hormone concentration tested that significantly enhanced MeAIB uptake in nonseptic muscle was 10(2) microU/mL and in septic muscle 10 microU/mL . The results suggest that sepsis in rats specifically inhibits amino acid transport system A and that reduced muscle amino acid uptake may be caused by a circulating factor in sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

J Hosp Infect, 1990 Apr, 15(3), 283 - 6
A comparison between imipenem and metronidazole prophylaxis against sepsis following appendicectomy; Burkitt DS et al.; A single preoperative dose of imipenem/cilastatin was compared with metronidazole for the prevention of infectious sequelae following emergency appendicectomy . Patients with established sepsis received in addition 72 h of either intravenous imipenem or ampicillin, gentamicin and metronidazole postoperatively . Two hundred and sixty-eight patients were studied . Wound infection rate in low-risk patients was 9% for metronidazole and 8% for imipenem . When sepsis was already established intraperitoneally the wound infection rate was 24% for the triple therapy regimen and 8% for imipenem . There was no statistically significant difference between the infection rates in the two groups of treatment whatever the state of the appendix, but there was a trend in favour of imipenem in those patients with a perforated appendix.

Arch Surg, 1990 Apr, 125(4), 531 - 6
Sepsis, signals, and surgical sequelae (a hypothesis); Michie HR et al.; Cytokines, products of the bodies on cells, are the major signals that orchestrate the host's response to bacterial infection . Those signals generated following infection include interleukins 1, 2, and 6, interferon gamma, and tumor necrosis factor (or cachectin) . Tumor necrosis factor is the only cytokine, to date, that has been shown to fulfill Koch's postulates and, thus, be casually related to host responses . Host responses to cytokines vary because of alterations in the genetic mechanism that controls cytokine production, because of an alteration in the responsiveness of the reticuloendothelial system at the time of signal induction and because of alterations in cell surface receptors . Only now are techniques evolving that can detect cytokine concentrations or production rates to relate these molecules to varying aspects of human disease . A major therapeutic goal in the future will be directed toward blocking the deleterious effects of cytokines while maintaining their protective or beneficial effects.

Masui, 1990 Mar, 39(3), 367 - 71
{Reduction in leukocyte elastase levels in patients with sepsis by administration of urinastatin}; Hiraoka N et al.; Leukocyte elastase (LE) plays a role in the development of shock . Therefore, we examined the effects of urinastatin, a protease inhibitor, on LE in 7 patients with sepsis . LE levels before the administration of urinastatin were high in all patients, especially those in shock . Administration of urinastatin markedly decreased LE levels, with the decrease being more remarkable in patients showing high LE levels before treatment . These results suggest that urinastatin not only reduces LE levels but also suppresses factors that are involved in the development of septic shock.

Am J Physiol, 1990 Mar, 258(3 Pt 2), H625 - 33
Sepsis-induced diastolic dysfunction in chronic canine peritonitis; Stahl TJ et al.; A chronic canine model of hyperdynamic sepsis was achieved by cecal ligation and puncture (SEP) in conjunction with continuous high-volume fluid resuscitation . Cardiac function was evaluated using ultrasonic cardiac crystals placed across the major, minor, and wall thickness axes of the left ventricle, together with simultaneous arterial and ventricular pressure measurement . Seven to 10 days after crystal implantation, animals were randomized to either SEP (n = 10) or sham laparotomy control (n = 7) . SEP dogs became febrile and lethargic, with elevated leukocyte counts and positive blood cultures for enteric organisms . They were also hyperdynamic, with significant increases in heart rate and cardiac output and a fall in systemic vascular resistance . Systolic blood pressure, stroke volume, and ejection fraction remained stable . Relative to control, the SEP group demonstrated a significant reduction in intrinsic contractility during systole, as measured by the heart rate and load-independent index of left ventricular performance Emax (P less than 0.01), confirming the observations of others . In addition, however, diastolic function also became markedly abnormal with a progressive increase in unstressed and end-diastolic ventricular volumes (P less than 0.05) and a significant decrease in myocardial compliance as quantitated by transmural pressure vs . volume-strain analysis . It is hypothesized that this increase in diastolic volume helps to maintain global cardiac performance during the hyperdynamic response to sepsis in the presence of adequate volume support.

Surgery, 1990 Mar, 107(3), 295 - 301
Hepatic blood flow and splanchnic oxygen consumption measurements in clinical sepsis; Dahn MS et al.; In an effort to characterize the hemodynamic response of the liver to sepsis, hepatic blood flow (HBF) was measured in 10 normal volunteers and compared with that of 9 patients with sepsis . Flow was determined according to two different indicators and three methods of analysis including indocyanine green dye clearance (HBFICG), galactose clearance (GC), and galactose clearance with splanchnic galactose gradient measurement (HBFGG) . For normal subjects, these three analytic methods provided essentially identical results (HBFICG = 0.74 +/- 0.18, GC = 0.72 +/- 0.14, and HBFGG = 0.76 +/- 0.16 L/min-m2) . With hepatic venous sampling, HBF in patients with sepsis was significantly higher than normal levels (HBFICG = 1.28 +/- 0.50 and HBFGG = 1.17 +/- 0.52 L/min-m2) (p less than 0.025), but HBF by the GC technique (0.89 +/- 0.41 L/min-m2), which uses peripheral venous sampling, was not significantly increased because of reduced splanchnic galactose extraction, which appears to be characteristic of sepsis . Thus HBF estimates based on peripheral venous sampling must be interpreted with caution in view of the reduced extraction fraction in sepsis . HBF in clinical sepsis tends to increase in response to this inflammatory stress.

J Nucl Med, 1990 Mar, 31(3), 311 - 5
Comparison of technetium-99m-HM-PAO leukocytes with indium-111-oxine leukocytes for localizing intraabdominal sepsis; Mountford PJ et al.; Technetium-99m-HM-PAO {( 99mTc}HM-PAO) leukocyte and indium-111-oxine (111In-oxine) leukocyte scanning were carried out simultaneously in 41 patients at 4 hr and 24 hr after reinjection to determine whether the 4-hr 99mTc scan could replace the 24-hr 111In scan for detecting intraabdominal sepsis . Abdominal infection was confirmed in 12 cases . The 4-hr 99Tc-leukocyte scan, the 4-hr 111In-leukocyte scan, and the 24-hr 111In-leukocyte scan yielded a sensitivity of 100%, 67%, and 100%, respectively, and a specificity of 62%, 90%, and 86%, respectively . The 24-hr 99mTc-leukocyte scan also produced a sensitivity of 100%, but it was falsely positive in all 29 cases without infection due to physiologic bowel uptake . False-positive 4-hr 99mTc-leukocyte scans were also produced by physiologic bowel uptake in seven cases all of whom had true-negative 4-hr and 24-hr 111In-leukocyte scans . Because of the high incidence of false-positive 4-hr {99mTc}HM-PAO leukocyte scans, it was concluded that they could not replace 24-hr 111In-leukocyte scans for detecting intraabdominal sepsis, and that serial 99mTc leukocyte scans starting earlier than 4 hr after reinjection must be evaluated.

Ann Trop Paediatr, 1990 Mar, 10(1), 35 - 7
Complement components in neonatal sepsis; Singh RP et al.; Complement components C3, C1q, factor B and breakdown products of C3, i.e . C3c and C3d, were evaluated in the diagnosis and prognosis of sepsis in 24 neonates with proven sepsis . The complement components were measured by electroimmunodiffusion and breakdown products by counterimmunoelectrophoresis (CIEP) . The babies with sepsis were found to have decreased levels of C1q and factor B as compared with suitably matched healthy controls . No statistically significant depression was observed in C3 levels of infected babies . However, breakdown products of C3, i.e . C3c and C3d, were detected in 58.3% of these babies . The breakdown products of C3 were not present in any of the healthy controls . The degree of depression of complement components was of no prognostic significance in neonatal sepsis.

Br J Surg, 1990 Feb, 77(2), 199 - 203
Effect of acute starvation on plasma fibronectin response to sepsis; Cheslyn-Curtis S et al.; There is evidence that undernutrition may contribute to the reduction in plasma fibronectin concentration and the depression of the reticuloendothelial (RE) system associated with severe sepsis . We have investigated the effects of fasting, surgical trauma and sepsis on plasma fibronectin concentrations and RE function . In experiment 1, plasma fibronectin was measured in rabbits (n = 14) before and 48 h after fasting . In experiment 2, sepsis was induced by devascularization of the appendix in animals on a normal diet (sepsis group, n = 7) . A third group of animals underwent only a laparotomy (laparotomy only group, n = 7) . Plasma fibronectin concentrations and the blood clearance and organ distribution of 99mtechnetium tin colloid (TTC) were measured 24 h after operation . Compared with pooled reference plasma, fasting in experiment 1 resulted in a reduction in mean(s.e.m.) plasma fibronectin concentration from 98(1.5) per cent to 86(3.7) per cent (T = 2, P less than 0.005) . Mean(s.e.m.) plasma fibronectin concentration was raised in the sepsis group to 117(4.6) per cent, compared with 97(2.5) per cent in the laparotomy only group (U = 5, P less than 0.02), but there was no such increase in the fasting and sepsis group . There was a delay in the blood clearance and reduced hepatic uptake of TTC in both sepsis groups . The dissociation between fibronectin concentrations and RE function in animal models of sepsis casts doubt on the importance of fibronectin in RE function.

Circ Shock, 1990 Feb, 30(2), 107 - 15
Unmeasured anion during severe sepsis with metabolic acidosis; Rackow EC et al.; It is assumed that the development of metabolic acidosis during sepsis is secondary to lactic acidosis . We assessed the composition of the anion gap during severe sepsis induced by cecal perforation in rats . In the first experiment, cardiac output, arterial blood gases, and arterial lactate were measured over a 6 hr interval in five septic rats and in five rats serving as sham-operated controls . The cardiac output decreased from 331 +/- 32 to 172 +/- 9 ml/kg/min (P less than 0.01) in the septic rats . Although the arterial lactate was increased to 2.1 +/- 0.2 mEq/L in septic rats compared to 0.8 +/- 0.1 mEq/L in sham rats (P less than 0.01), the HCO3- was decreased to 16.5 +/- 0.6 mEq/L in septic rats versus 23.8 +/- 1.10 mEq/L in sham rats (P less than 0.01) . We further investigated this bicarbonate deficit in a second study in which arterial blood was sampled at 6 hr for blood gases, and plasma Na+, K+, Cl-, HCO3-, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, citrate, creatinine, albumin, and amino acids in five septic and five sham rats . The serum anion gap was calculated as {(Na(+) + K+) - (Cl(-) + HCO3-)} . The anion gap was 21.6 +/- 1.6 mEq/L in the septic animals as compared to 13.2 +/- 0.5 mEq/L in the sham animals (P less than 0.01) . There were no differences in the concentration of pyruvate, beta-hydroxybutyrate, acetoacetate, citrate, creatinine, albumin, or amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Burns, 1990 Feb, 16(1), 9 - 12
Effect of prostaglandin E in multiple experimental models . VII . Effect on resistance to sepsis; Waymack JP et al.; The immunosuppression seen following burn injury has frequently been attributed to elevated prostaglandin E levels . We evaluated the contribution of elevated prostaglandin E levels on susceptibility to infectious complications utilizing multiple mouse models . The administration of 100 micrograms/kg of the long-acting derivative of prostaglandin E, 16,16-dimethyl-prostaglandin E, was found to improve survival in C3/HEN mice challenged with 1 x 10(8) Escherichia coli organisms intraperitoneally . The administration of indomethacin was found to decrease survival in the same model . With C3/HEJ (endotoxin-resistant) mice, indomethacin was found to increase mortality rates in animals challenged with 1 x 10(8), 1 x 10(9) or 1 x 10(10) Escherichia coli organisms . These findings suggest that elevated prostaglandin E levels seen in burn patients may not be responsible for the postburn increased susceptibility to infectious complications.

Eur J Pediatr, 1990 Feb, 149(5), 351 - 3
Total parenteral nutrition associated cholestasis: a predisposing factor for sepsis in surgical neonates?
Bos AP, Tibboel D, Hazebroek FW, Bergmeijer JH, van Kalsbeek EJ, Molenaar JC.
Of 496 neonates and infants less than 1 year of age admitted to the paediatric surgical intensive care unit (PSICU) over a 5 year period (1983-1987), 94 required total parenteral nutrition (TPN) for more than 14 consecutive days, generally due to congenital anomalies of the digestive tract . Cholestasis occurred in 15 of them and 12 of these patients developed sepsis . In contrast, of the 79 patients on TPN that remained free from cholestasis, only 23 developed sepsis . The mortality rate for the TPNAC-group was substantially higher than for the group without TPNAC . It is suggested that development of TPNAC might lead to impairment of non-specific cellular immunity in neonates.

J Pharmacol Exp Ther, 1990 Feb, 252(2), 675 - 82
Supersensitivity and changes in the active population of beta adrenoceptors in rat right atria in early sepsis; Barker LA et al.; We have investigated the effect of sepsis induced by cecal ligation and puncture on the chronotropic actions of beta adrenoceptor agonists on isolated right atria . The present findings show that right atria obtained from rats in an early stage of sepsis were supersensitive to the chronotropic actions of the beta-agonists, isoproterenol (ISO), fenoterol (FEN) and prenalterol (PREN) . The supersensitivity to the chronotropic actions of ISO and FEN was much greater than that which developed to PREN . The positive chronotropic actions of isobutylmethylxanthine and forskolin were not affected by sepsis . The receptor subtypes mediating the responses to ISO, FEN and PREN by control and septic right atria were characterized by functional assays using selective beta-1 and beta-2 antagonists . The results showed that the chronotropic response produced by all three agonists on right atria obtained from control rats were mediated by beta-1 receptors . In contrast, the chronotropic actions of ISO and FEN on atria from septic rats were mediated by what appears to be beta-2 receptors and those of PREN by beta-1 receptors.

Med Clin (Barc), 1990 Jan 20, 94(2), 58 - 60
{Sepsis caused by Candida parapsilosis . Joint and lung involvement in 2 patients with acute leukemia}; Salo J et al.; Sepsis due to Candida parapsilosis with involvement of the joints and the lungs, respectively, is reported in two patients with acute leukemia . The first patient had ankle arthritis 72 days after an allogenic bone marrow transplant for acute lymphoblastic leukemia . The second patient had pneumonia with cavitation during pancytopenia after chemotherapy for acute monocytic leukemia . In both cases, C . parapsilosis sepsis responded to therapy with amphotericin B, associated with miconazole in the first patient and with 5-fluorocytosine in the second one . The rarity of septic foci during C . parapsilosis fungemia and the good outcome of both patients are emphasized . This good result was probably due to early antifungal therapy and the relatively rapid recovery of granulocytopenia.

J Pediatr Surg, 1990 Jan, 25(1), 117 - 9
Improvement in catheter sepsis rate in burned children; Askew AA et al.; Routine frequent central venous catheter (CVC) changes in burned patients (either change in insertion site or change over guidewires) has been advocated to decrease catheter-related sepsis . The need for this management has not been verified for children with burns . We reviewed our pediatric burn population with regard to CVC sepsis rate and individual CVC longevity to confirm this traditional policy . From 1978 to 1988, 70 children admitted to the Children's Hospital of Oklahoma Burn Unit required central venous access . Patients in whom CVCs were changed frequently (FC), (n = 10; no . of CVC, 46) were compared with those in whom CVCs were changed only for mechanical complications or sepsis (NFC), (n = 60; no . of CVC, 74) . There were 10 septic CVCs in each group . The difference in mean length of individual CVC use between FC and NFC was significant (4.6 v 17.7 days; P less than .01) . The difference in the number of septic CVCs per total number of catheter days in each group was highly significant (FC: 10 CVC/212 d . = 0.05; NFC: 10 CVC/1,112 d = 0.009; P less than .001) . This study demonstrates a significant decrease in catheter-related sepsis when CVCs are not changed on a routine frequent basis.

Crit Care Clin, 1990 Jan, 6(1), 121 - 46
Sepsis and the trauma patient; McGuire GP et al.; Conventional therapy for septic shock concentrates on correcting circulatory perfusion defects by optimizing hemodynamic parameters and oxygen delivery to the periphery . In the face of ongoing sepsis, the central abnormality of nutrient acquisition and energy production at the cellular level remains and the patient often progresses to MSOF despite our best efforts . Currently, surgical drainage and antibiotic therapy are the mainstays for eradication of infection . In the future, as we understand more of the mediators and metabolic consequences of septic shock, we anticipate that a more specific, directed therapy will be developed to reduce the high mortality rate.

Am J Physiol, 1990 Jan, 258(1 Pt 2), R21 - 31
Sepsis does not alter red blood cell glucose metabolism or Na+ concentration: a 2H-, 23Na-NMR study; Hotchkiss RS et al.; The effects of sepsis on intracellular Na+ concentration ({Na+}i) and glucose metabolism were examined in rat red blood cells (RBCs) by using 23Na- and 2H-nuclear magnetic resonance (NMR) spectroscopy . Sepsis was induced in 15 halothane-anesthetized female Sprague-Dawley rats by using the cecal ligation and perforation technique; 14 control rats underwent cecal manipulation without ligation . The animals were fasted for 36 h, but allowed free access to water . At 36 h postsurgery, RBCs were examined by 23Na-NMR by using dysprosium tripolyphosphate as a chemical shift reagent . Human RBCs from 17 critically ill nonseptic patients and from 7 patients who were diagnosed as septic were also examined for {Na+}i . Five rat RBC specimens had {Na+}i determined by both 23Na-NMR and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) . For glucose metabolism studies, RBCs from septic and control rats were suspended in modified Krebs-Henseleit buffer containing {6,6-2H2}glucose and examined by 2H-NMR . No significant differences in {Na+}i or glucose utilization were found in RBCs from control or septic rats . There were no differences in {Na+}i in the two groups of patients . The {Na+}i determined by NMR spectroscopy agreed closely with measurements using ICP-AES and establish that 100% of the {Na+}i of the RBC is visible by NMR . Glucose measurements determined by 2H-NMR correlated closely (correlation coefficient = 0.93) with enzymatic analysis . These studies showed no evidence that sepsis disturbed RBC membrane function or metabolism.

Arch Surg, 1990 Jan, 125(1), 36 - 40; discussion 40-1
Kupffer cell blockade increases mortality during intra-abdominal sepsis despite improving systemic immunity; Callery MP et al.; The effect of Kupffer cell (KC) blockade on systemic immunity during intra-abdominal sepsis was evaluated . Gadolinium chloride, a rare earth metal, reduced KC phagocytosis by 75% when it was given to BALB/c mice for 2 days . Thereafter, control mice and mice with KC blockade underwent either a sham operation or a cecal ligation and puncture . As indicators of systemic cell-mediated immunity, delayed-type hypersensitivity responses to soluble antigen and cellular alloantigen were measured 24 hours after the abdominal operations . The activation of KCs was assessed by their in vitro interleukin 1 production . Control septic mice were profoundly immunosuppressed and demonstrated marked KC activation . Septic mice with KC blockade, however, demonstrated less systemic immune hyporesponsiveness and significantly reduced KC activation, but died more rapidly . We concluded that despite apparent improvement in systemic immunity by KC blockade during intra-abdominal sepsis, the resulting impairment in functional phagocytic integrity predisposes to significantly higher mortality.

Intensive Care Med, 1990, 16 Suppl 3, S187 - 91
A model for the interplay of inflammatory mediators in sepsis--a study in 48 patients; Hack CE et al.; Previously we studied levels of the cytokine IL-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis . Some of these inflammatory parameters appeared to be associated with a poor prognosis . Here we report on the relationships of C4a and C3a (complement activation products), of factor XII and prekallikrein (contact system proteins), of elastase (a protease released by activated neutrophils) and of the cytokine IL-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the Intensive Care Unit . No significant correlations between any inflammatory parameter and either systemic vascular resistance or cardiac index were found . Mean arterial pressure significantly correlated with both factor XII and prekallikrein levels . Lactate correlated with C3a and C4a, with elastase, and in particular, with IL-6, whereas it did not correlate with either factor XII or prekallikrein . Platelet numbers inversely correlated with both C3a and C4a, as well as with elastase and IL-6, whereas they positively correlated with factor XII and prekallikrein . Based on these findings we propose a model for the interplay of these inflammatory mediators in the pathogenesis of sepsis . This model takes into consideration the occurrence of capillary leakage, shock, disseminated intravascular coagulation, thrombocytopenia and of acute phase reactions in sepsis.

Padiatr Grenzgeb, 1990, 29(5), 363 - 71
{Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis . 2: Immunotherapy}; Borte M et al.; The physiological immunodeficiency of preterm and term newborns is the major cause of their increased susceptibility to infections . Although nonspecific and specific host defence mechanisms are morphologically intact, there are functional and quantitative defects . Supportive immunotherapy is required to equalize these immunological defects . This article reviews topical possibilities for immunotherapy of neonatal sepsis (exchange transfusion, transfusion of fresh blood or fresh plasma, granulocyte transfusion, use of immunoglobulins, fibronectin, interferon and colony-stimulating factor).

Clin Ther, 1990, 12 Suppl B, 21 - 33
The treatment of sepsis and other complications in the trauma patient; Trunkey DD; Immediate complications of trauma and shock include right heart failure, acute respiratory distress syndrome, coagulopathy, brain edema, small bowel dysfunction, renal failure, and immune dysfunction . Nosocomial infections are also common in trauma patients . These infections are the combined result of a compromised host defense and various iatrogenic risk factors, including the use of percutaneous drainage tubes, malnutrition, the injudicious use of prophylactic antibiotics, and treatment staff hygiene . The use of prophylactic antibiotics appears to be unwarranted in head, maxillofacial, and neck injuries and is debatable in chest and soft-tissue wounds, fractures, and injuries of the peritoneal cavity . The use of antibiotics in small bowel and colon injuries is justified . Antibiotics are necessary in crush or avulsive injuries . Combination antibiotic therapy often results in multiple complications that may compound the patient's problems . Therefore, a single antibiotic with minimal side effects is the therapy of choice in the surgical intensive care unit.

Arch Surg, 1990 Jan, 125(1), 70 - 4; discussion 74-5
Enhanced susceptibility to sepsis after simple hemorrhage . Depression of Fc and C3b receptor-mediated phagocytosis; Ayala A et al.; To determine whether phagocytosis mediated by Fc receptors and/or receptors for the third component of complement (C3b) are altered after hemorrhage, C3H/HeN mice were subjected to nonlethal hemorrhage and then adequately resuscitated . Twelve hours after the hemorrhagic episode, a significant decrease in both Fc (-55.2%) and C3b (-46.6%) receptor-positive peritoneal macrophages was observed compared with controls . At 24 hours the extent of the depression, while still marked, was only -22.5% and -17.4% for Fc and C3b receptors, respectively . By day 3 after hemorrhage, no differences could be observed for either of these receptors . The capacity of macrophages from mice after hemorrhage to elaborate interleukin 1 or tumor necrosis factor-alpha showed no increase over that of the sham controls, and serum levels of endotoxin were not elevated 2 or 24 hours after hemorrhage . Moreover, endotoxin-tolerant C3H/HeJ mice also exhibited depression of both receptors after hemorrhage . Thus, the inability of the host macrophages to clear opsonized infectious agents after hemorrhage may be due in part to the loss of Fc and C3b receptors on macrophages.

Transfus Med Rev, 1990 Jan, 4(1), 14 - 22
The use of granulocyte transfusion in neonatal sepsis; Cairo MS; Many questions are raised in this review about the role of adult donor granulocyte transfusions in the setting of overwhelming bacterial neonatal sepsis . There clearly exists a number of variables, which influence the survival and morbidity associated with bacterial sepsis . The important differences in these studies highlight the need for prospective large multicenter studies to definitely clarify these issues . Important criteria, which are yet to be established and which impact significantly, include the time of administration of adjuvant granulocytes, the number of granulocytes that need to be harvested, which group of neonates require early granulocyte transfusions, the best method for optimal and easy granulocyte collection, the frequency and intervals of granulocyte transfusions, and improved methods for the early identification of neonatal candidates who would benefit from the granulocyte transfusions . The benefits of granulocyte transfusions (ie, the improvement in morbidity and mortality) in septic neutropenic neonates must be weighed against the possible and reported side effects associated with such transfusions . Adverse reactions including graft-versus-host disease, CMV, HIV and hepatitis infection, fluid retention and pulmonary edema, blood group sensitization, and pulmonary insufficiency may all result from the use of granulocyte transfusions in a host who has evidence of developmental immaturity . All future studies must continue to evaluate these potential complications to balance and analyze the true benefits of survival with reported treatment results . Recently, a number of investigators including ourselves, have begun to examine the role of alternate adjuvant immunotherapy in enhancing neonatal host defense in the clinical setting of overwhelming bacterial sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

J Perinat Med, 1990, 18(3), 157 - 63
Evaluation of C . reactive protein values in neonatal sepsis; Shortland DB et al.; C . reactive protein (CRP) estimations were performed prospectively on 30 consecutive admissions of very low birth weight infants to a Regional neonatal intensive care unit . The samples were analysed by a recently described, rapid intralipid agglutination assay and by a reference turbidimetric technique . Two hundred and ninety samples were assayed by both techniques . The intralipid agglutination was positive on two occasions when the reference method found normal levels . No false negative reactions occurred . Bacterial micro-organisms were isolated on 32 occasions but 19 of the organisms were considered to represent bacterial colonisation or contamination . The CRP remained negative in 17 cases . There were 13 episodes of clinical deterioration associated with positive bacterial cultures . In each of the six infants with severe systemic infections (septicaemia (4), meningitis (1), and osteomyelitis (1)), the levels were raised . In five of these infants the CRP was elevated before, or at the time of, the clinical deterioration . The CRP remained normal during seven (54%) of the culture positive events . We believe that the CRP estimations provide additional information in the evaluation of the infant with suspected sepsis . Serial measurements are helpful in distinguishing bacterial contamination from invasive infection but are not helpful in predicting infection during the pre-clinical phase . The intralipid agglutination technique is a rapid and reliable test and could be performed on the neonatal unit outside normal laboratory hours.

Eur J Nucl Med, 1990, 16(4-6), 307 - 9
Indium 111 leucocyte scintigraphy in abdominal sepsis . Do the results affect management?
Baba AA, McKillop JH, Cuthbert GF, Neilson W, Gray HW, Anderson JR.
We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis . The sensitivity was 95% (21/22) and the specificity was 91% (21/23) . Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%) . In 3, the study results were misleading and led to inappropriate treatment . Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based.

J Lab Clin Med, 1990 Jan, 115(1), 52 - 61
Flow cytometric parameters of neutrophil function as early indicators of sepsis- or trauma-related pulmonary or cardiovascular organ failure; Rothe G et al.; Flow cytometric parameters of neutrophil function, such as phagocytosis and degradation of Escherichia coli, intracellular pH value, esterase activity, and cell volume, were evaluated as risk indicators for sepsis- and trauma-related pulmonary and cardiovascular organ failure in intensive care patients . Serial blood samples (n = 201) were obtained from 47 prospectively identified patients . Each patient's condition was classified daily within four categories: post-traumatic (n = 22) or septic (n = 28) organ failure, transition state (n = 119), and stable organ function after recovery (n = 27) . Thirty-two parameters of neutrophil function were automatically calculated for each blood sample from several flow cytometric list mode measurements of cell samples vitally stained with acridine orange for intact and denatured DNA or with 1,4-diacetoxy-2,3-dicyanobenzene for intracellular pH and esterase activity . The DNA of dead cells was simultaneously counterstained with propidium iodide . The cell biochemical parameter pattern was significantly different among samples of patients from the four clinical categories (p less than 0.05) . Hyperergic phagocytosis was observed after trauma, in contrast to hypoergic phagocytosis, increased neutrophil cell volume, and elevated intracellular pH during sepsis . The clinical categories were correctly identified in 82% of the samples by automated classification with the DIAGNOS1/SPSS program system from the flow cytometrically determined cell functions . The course of the disease was correctly predicted 3 days in advance to the clinical manifestation of pulmonary or cardiovascular organ failure in 92% of the samples . The multifunctional analysis of neutrophils by flow cytometry seems of interest for early medical intervention in preseptic and preshock patients.

Crit Care Med, 1990 Jan, 18(1), 32 - 6
Relationship of plasma cholesterol level to doses of branch-chain amino acids in sepsis; Chiarla C et al.; Plasma cholesterol levels, plasma lactate, and total body RQ were measured in septic patients undergoing total parenteral nutrition (TPN) with glucose, fat, and two different branch-chain amino acid admixtures (49% BCAA and 16% BCAA) . Mean plasma cholesterol for all measurements (2.61 +/- 0.94 {SD} mmol/L) was lower than normal; however, it was higher with 49% BCAA than with 16% BCAA (2.94 +/- 0.95 vs . 2.27 +/- 0.81 mmol/L, p less than .001) for comparable loads of glucose, fat, and total amino acids . Plasma lactate and RQ were lower with 49% BCAA than with 16% BCAA (p less than .001 for both) . Cholesterol was directly related to the absolute dose of BCAA (p less than .001), was unrelated to the dose of non-BCAA, and was inversely related to lactate (p less than .001) . These results suggest that BCAA ketoacids contribute to cholesterol synthesis in sepsis, as well as being an oxidative source . The data also suggest that the reduction in alanine in BCAA-enriched amino-acid TPN assists in the lowering of plasma lactate secondary to abnormal septic glucose metabolism.

Z Exp Chir Transplant Kunstliche Organe, 1990, 23(4), 213 - 6
{Immunoglobulin therapy of postoperative sepsis}; Wesoly C et al.; 35 patients with septic postoperative complications entered a prospectively randomized study . The clinical state of these patients was daily determined using the sepsis score described by Elebute and Stoner . Endotoxin and antithrombin III were measured in the plasma using the limulus-amoebocyte-lysat test for endotoxin determination . The septic patients were treated with an immunoglobulin preparation (Pentaglobin) administered by the intravenous route . This preparation is enriched in IgM and IgA . Due to the immunoglobulin therapy the endotoxin titres decreased; simultaneously a reduction of mortality and shortening of time of hospitalization and of mechanical ventilation were observed.

Acta Physiol Hung, 1990, 75(4), 303 - 20
A canine model of hyperdynamic sepsis induced by intestinal ischemia; Nagy S et al.; A hyperdynamic sepsis model was developed in dogs . It is based on a 3-hour clamping of the arteries supplying the middle portion of the jejunum . The ensuing sepsis has a course of several days, during which the animals were studied in the conscious state . 2/3 of the animals developed a sustained 32-108 per cent increase in cardiac output, and survived 7 days or more . In the other 1/3 of the animals, the cardiac output was lower than the control value and all these animals died within 5 days . There were no differences between the two groups in other parameters examined . Sepsis caused a steady, slight decrease in mean arterial pressure, an increase in heart rate, and leukocytosis . The plasma levels of epinephrine and norepinephrine showed a sustained, significant elevation . The level of thromboxane B2 was high only on the first day of sepsis, and that of plasma renin activity on the first 2 days . Necrosis and edema of jejunal villi were demonstrated histologically in the early period . Hemocultures were positive in only 5 of 11 animals examined, suggesting the predominant role of absorbed toxins . This model simulates human sepsis well and is suitable for the study of pathophysiologic mechanisms in hyperdynamic sepsis.

Thromb Res, 1989 Dec 15, 56(6), 731 - 7
Influence of plasma protease activation on electroimmunoassay and nephelometry of plasma fibronectin in sepsis; Hesselvik F et al.; In vitro experiments have shown that proteases such as trypsin, kallikrein and plasmin may split plasma fibronectin, yielding changes in apparent mass concentration, i.e.: a decrease when using immunonephelometry (IN), and an increase when using electroimmunoassay (EIA) . In the present in vivo study, plasma from 49 patients with severe infections was assayed for fibronectin by IN and EIA, and for prekallikrein, plasminogen and antithrombin . In patients with normal prekallikrein (n = 26) and plasminogen (n = 23), the agreement between the two fibronectin assay methods was good (ratio EIA/IN = 0.99 +/- 0.06); a similar good agreement was found in 45 healthy blood donors (ratio 0.97 +/- 0.02) . In contrast, the 20 patients with low prekallikrein showed fibronectin values that were significantly higher by EIA than by nephelometry (ratio 1.27 +/- 0.10, p less than 0.01) . Similarly, the 26 patients with low plasminogen had a significantly increased ratio (1.21 +/- 0.09, p less than 0.05) . No such difference was seen, however, between patients with low or normal antithrombin . Thus, kallikrein and plasmin activation in vivo appear to increase the fibronectin concentration measured by EIA, possibly due to the formation of small fragments with increased electrophoretic motility.

Am J Physiol, 1989 Dec, 257(6 Pt 2), R1265 - 81
Myocardial function in sepsis and endotoxin shock; Abel FL; Myocardial function in sepsis and endotoxin shock is reviewed . Clinical, whole animal, and isolated tissue studies are compared to answer the question whether sepsis and/or endotoxin directly damage the myocardium . Myocardial performance is considered relative to control of preload, afterload, and heart rate . Despite the fact that these vary widely in different studies, there is overwhelming evidence that myocardial performance is depressed in both sepsis and endotoxin shock . The depression is dose related, occurs early after large doses of endotoxin but may follow a hyperdynamic phase in sepsis or after low doses of endotoxin . Endotoxin itself does not appear to be the depressant factor; the final depressant substance(s) is unknown . Calcium transport by the sarcoplasmic reticulum is depressed . This defect is more prominent in the endocardium than in the epicardium . Myocardial adenosinetriphosphatase (ATPase) and norepinephrine stores may be depleted . The septic myocardium has an increased dependence on sympathetic nerve stimulation . There is little evidence that the cause of the myocardial depression is an inadequate coronary blood flow.

Circ Shock, 1989 Dec, 29(4), 361 - 70
Fatty acid metabolism in the heart during Escherichia coli sepsis in the rat; Lanza-Jacoby S et al.; Fatty acid metabolism was studied in fasted control, fasted Escherichia coli-treated, fed control, and fed E . coli-treated rats to find out whether the reduction in myocardial carnitine was associated with changes in oxidation and esterification of long chain fatty acids . Rats were made septic by injecting i.v . 8 X 10(7) live colonies of E . coli per 100 g body weight . Fed rats were infused intragastrically with a nutritionally adequate diet containing glucose plus fat for five days before inducing sepsis . Food was removed from the fasted rats after E . coli injection . Twenty-four hours later, the production of CO2 from {1-14C}palmitate was not altered in heart homogenates from fasted or fed E . coli-treated rats . In comparison to control rats, heart homogenates from fasted E . coli-treated rats incorporated 32% more {1-14C}palmitate into triglycerides . The heart content of triglycerides was also increased threefold during sepsis . Rates of esterification and lipid composition were not altered in the hearts from fed E . coli-treated rats . The increased rate of triglyceride synthesis in the hearts from fasted E . coli-treated rats appears to be due to a 40% higher content of glycerol 3-phosphate and 55% more activity of glycerol 3-phosphate acyltransferase . These results also suggest that the reduced content of myocardial carnitine that occurs during E . coli sepsis does not limit the availability of fatty acids for oxidation.

Surg Gynecol Obstet, 1989 Dec, 169(6), 568 - 75
Cytokines, sepsis and the surgeon; Brown JM et al.; Trauma and infection cause complex neuroendocrine responses . Afferent nervous stimuli, stimuli from the central nervous system, local wound factors and endocrine changes characterized by increases in stress hormones are some of these responses . Molecular biology has launched us into an age in which the categorization of these neuroendocrine changes will be broadened to include the profound effects of previously unidentified molecules . TNF and IL-1 are two protein hormones of the cytokine family . TNF causes hemorrhagic necrosis of solid tumors, mediates the lethal effects of endotoxemia and induces immune metabolic and intercellular changes . IL-1 is a mediator of inflammation and the acute phase response . The diversity of actions of TNF and IL-1 appear to be results of their multiple forms (alpha and beta) and their abilities to act both as membrane-associated and free proteins, to act locally (paracrine) as well as systemically, to act synergistically and to be involved in complex webs of self-promotion and amplification . On the basis of these diverse capabilities, they are prime candidates to be mediators of common surgical disease.

J R Coll Surg Edinb, 1989 Dec, 34(6), 314 - 5
Intraperitoneal placement of gentamicin beads in the management of prosthetic graft sepsis; Reilly DT et al.; A simple and non-hazardous technique for intraperitoneal placement of gentamicin beads after excision of an infected prosthetic aortic graft is presented . It has been used successfully in six cases of aortic graft sepsis.

Am J Physiol, 1989 Dec, 257(6 Pt 1), C1055 - 61
An in vivo examination of rat brain during sepsis with 31P-NMR spectroscopy; Hotchkiss RS et al.; Neurological symptoms including lethargy, obtundation, and confusion are early and common findings in patients with sepsis . The etiology of the mental status changes that occur during severe infection is not known . We investigated the effects of sepsis on the levels of high-energy phosphates to determine whether decreased energy metabolism was a factor in the depressed neurological state . The time course of changes in brain pH and brain high-energy phosphate metabolites during an Escherichia coli infusion was determined from sequential phosphorus-31 nuclear magnetic resonance (31P-NMR) spectra of ketamine-xylazine-anesthetized rats . A second group of rats received 0.9% saline infusion and served as a control group . Despite severe obtundation and near loss of righting reflex, the rats in the septic group had no significant differences in the brain pH, the ratio of phosphocreatine (PCr) to beta-adenosine 5'-triphosphate (beta-ATP), or in the ratio of PCr to Pi . The only significant decrease in brain high-energy phosphates or pH occurred terminally in the septic rat group and corresponded with a rapidly falling arterial blood pressure . We conclude that the severe neurological depression that is characteristic of sepsis is not due to decreased levels of brain high-energy phosphates or brain acidosis.

Arch Surg, 1989 Dec, 124(12), 1386 - 9
The incidence of decreased red blood cell deformability in sepsis and the association with oxygen free radical damage and multiple-system organ failure; Machiedo GW et al.; We studied the incidence of decreased red blood cell deformability (RBCD) in sepsis and the association between decreased RBCD and oxygen free radical generation (as measured by malonyldialdehyde) and the occurrence of multiple-system organ failure (MSOF) . Patients were divided into three groups: septic (n = 28), nonseptic (n = 15), and control (n = 5) . Serial measurements of deformability index, malonyldialdehyde, and MSOF were made . The deformability index for the septic group (0.23 +/- 0.17) was significantly less than that for the nonseptic (1.12 +/- 0.48) and control (1.11 +/- 0.25) groups . The malonyldialdehyde levels for the septic group (4.5 +/- 1.0 nmol/mL) were significantly greater than those for the nonseptic (2.7 +/- 0.9 nmol/mL) and control (2.6 +/- 0.8 nmol/mL) groups . The MSOF index for the septic group (10.1 +/- 2.5) was significantly greater than that for the nonseptic (7.6 +/- 1.7) and control (6.0 +/- 0.0) groups . An inverse correlation existed between malonyldialdehyde and deformability index ( = .501, less than .001, n = 40) and between deformability index and MSOF index (= .350, less than .05, n = 61) . We conclude that RBCD is decreased during human sepsis; free radicals generated during sepsis may play a role in the decrease in RBCD . Decreased RBCD may contribute to the MSOF that occurs during sepsis.

J Pediatr, 1989 Dec, 115(6), 973 - 8
Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants: report of a pilot study; Clapp DW et al.; To evaluate the use of intravenously administered immune globulin (IVIG) for prevention of sepsis in preterm infants, we administered IVIG in a protocol designed to maintain a therapeutic serum "target level" of 700 mg/dl . The 200 patients who were eligible for the study (600 to 2000 gm birth weight) were monitored throughout their initial hospitalization . Of these, 115 patients were randomly assigned in a double-blind, controlled trial to treatment and placebo groups . The remaining 85 infants were not randomly assigned to a group, by parental request, but were followed and analyzed separately . In one patient who received IVIG, transient tachycardia and a decrease in blood pressure developed during an infusion; resolution occurred promptly after the infusion was discontinued . No persistent hepatic or renal abnormalities were noted in either the IVIG- or the placebo-treated group . There were seven episodes of sepsis in the placebo group and nine in the group whose parents refused consent to the study . No infant who received IVIG acquired nosocomial sepsis (p less than 0.01) . All patients in the placebo group in whom sepsis developed had serum IgG levels less than 400 mg/dl at the time sepsis developed . Serum IgG levels were maintained near 700 mg/dl in patients who received IVIG . These data indicate that administration of sufficient IVIG to maintain target serum IgG levels throughout hospitalization may decrease the incidence of nosocomial sepsis in preterm infants.

Rev Med Chil, 1989 Dec, 117(12), 1351 - 6
{Rhabdomyolysis caused by severe sepsis: discussion on its role in the development of acute renal failure}; Videla C et al.; Rhabdomyolysis was evaluated by measurement of total creatine kinase (CK) and lactic dehydrogenase (LDH) in 19 patients with severe sepsis; 12 developed acute renal failure (Group B) and 7 did not (Group A) . Results were compared to 7 patients with trauma (Group C) and 6 patients with chronic renal failure and minor infections (Group D) . CK was higher (p less than 0.005) in Group B than in A . Results in Group C were similar to those in A . Elevation of CK correlated to increases in creatinine (r = 0.655, p less than 0.005) . CK levels of Group D patients were lower than those of Group B . Blood pressure, lactate and pO2 were similar in both groups but thrombopenia was noted in Group B patients . Our results suggest that rhabdomyolysis and thrombopenia play a role in the development of renal failure in patients with severe sepsis.

Med Clin (Barc), 1989 Nov 25, 93(17), 660 - 2
{Lemierre's syndrome (post-anginal sepsis): a forgotten infection}; Garrido JA et al.; Publication Types:

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