Rev Infect Dis, 1987 Jul-Aug, 9 Suppl 4, S420 - 30 Plasma fibronectin and fibronectin therapy in sepsis and critical illness; Grossman JE; Plasma fibronectin may be an important component of host defense in critically ill patients, particularly after trauma and during sepsis . This paper reviews recent studies that have sought to characterize the natural history of plasma fibronectin during sepsis, as well as those studies that tested the effect of therapy with concentrated fibronectin in sepsis . The decrease in plasma fibronectin that generally is seen in humans during sepsis probably is due to many factors, and it has been difficult to produce a similar pattern in animal models . Depletion of plasma fibronectin is not a sensitive or specific predictor of imminent sepsis, and once sepsis is established, the concentration of plasma fibronectin is no more sensitive a predictor of mortality than are many other clinical markers . Early, uncontrolled trials of therapy with a fibronectin concentrate in patients with sepsis appeared to indicate a propitious effect on organ function . However, more recent controlled trials have failed to show a significant effect of therapy with fibronectin concentrate on either organ function or patient survival. Int J Clin Pharmacol Ther Toxicol, 1987 Jul, 25(7), 354 - 62 Pharmacokinetics of ceftazidime and netilmicin in patients with sepsis; Ganzinger U et al.; The pharmacokinetics of ceftazidime and netilmicin were evaluated under septicemic conditions . In a longitudinal study, both drugs were administered simultaneously (ceftazidime 2.0 g 20 min constant i.v . infusion and netilmicin 150 mg i.v . bolus injection) every 12 hours to patients who had a positive blood culture and hyperdynamic circulatory functions . Twenty-four hours after the first period of this pharmacokinetic study, identical parameters were evaluated under dipyrone induced normothermic conditions . The mean residence time and the volume of distribution was significantly altered during septicemia compared to normal conditions . With respect to the relative distribution properties ceftazidime tended to be distributed to a greater extent to the tissue compartment, whereas netilmicin showed an opposite behaviour . Beside significant correlations of absolute values, i.e . blood volume vs . volume of distribution, and relative values, i.e . total peripheral resistance vs . extraction rate, all other attempts failed to show any meaningful correlation . Owing to the heterogenous alterations of metabolic and hemodynamic functions and pharmacokinetic parameters, respectively, the data gained from this study do not allow any statistically validated conclusion regarding the pathophysiological mechanisms involved, although these findings are in accordance with animal experiments. JPEN J Parenter Enteral Nutr, 1987 Jul-Aug, 11(4), 345 - 53 Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycemic glucose clamp technique; White RH et al.; Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion . We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions . The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls . Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups . Forearm glucose uptake was similarly impaired . Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose . Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids . Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work . Norepinephrine showed no response to the glucose infusion in either group . Plasma glucagon concentrations were not significantly elevated in the septic patients . We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis . Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear. J Pediatr, 1987 Jun, 110(6), 935 - 41 Role of circulating complement and polymorphonuclear leukocyte transfusion in treatment and outcome in critically ill neonates with sepsis; Cairo MS et al.; We examined the effects of early administration of polymorphonuclear leukocyte (PMN) transfusions in neonates with sepsis by prospectively randomizing 35 consecutive critically ill infants with sepsis, 21 of whom received PMN transfusions in addition to supportive care, one transfusion every 12 hours for a total of five transfusions . Each transfusion consisted of 15 mL/kg containing 0.5 to 1.0 X 10(9) PMN with less than 10% lymphocytes, and was subjected to 1500 rads . PMNs were obtained by continuous-flow centrifugation leukopheresis . Pretreatment values that did not significantly affect survival included weight, gestational age, sex, prematurity, C-reactive protein, initial hematocrit, platelet count and absolute granulocyte count (AGC less than or equal to 1500/mm3), IgM, IgG, IgA, neutrophil supply pool depletion, hypoxia, acidosis, and hypotension . Postnatal age was significantly lower in the nontransfused group than in the transfused group; 2.3 +/- 0.6 vs 6.1 +/- 2.2, (P less than 0.001) . Positive blood cultures were obtained in 80% of both groups . Low circulating levels of total hemolytic complement were associated with a poor outcome and higher mortality: 56 +/- 4.0 IU in survivors vs 31 +/- 4.4 IU in nonsurvivors (P less than 0.01) . Survival was significantly greater in the PMN transfused group than in the nontransfused group: 20 (95%) of 21 vs nine (64%) of 14 (P less than or equal to 0.05) . No untoward effects were attributable to PMN transfusions, either during the study or on subsequent follow-up visits . These preliminary data suggest that early treatment with PMN transfusions improves survival in neonates with overwhelming sepsis . In addition, depleted or low circulating levels of complement may influence prognosis and thus future treatment strategies for neonatal sepsis. Arch Surg, 1987 Jun, 122(6), 702 - 6 Repeated laparotomy for postoperative intra-abdominal sepsis . An analysis of outcome predictors; Butler JA et al.; To identify factors modifying the outcome of reoperation for intra-abdominal infection, we analyzed the management of 47 patients who underwent repeated laparotomy from July 1980 through July 1985 . Overall mortality was 30% (14/47) . Factors predictive of death were as follows: age greater than 60 years (86% mortality vs 21% mortality), preoperative vs no organ failure (57% vs 6%), multiple vs single abscess (53% vs 16%), and exploratory vs directed operative approach (39% vs 17%) . Although the interval between the primary surgery and reoperation was similar between survivors (13 days) and nonsurvivors (14 days), five (36%) of 14 nonsurvivors were in septic shock and eight (57%) of 15 survivors showed evidence of organ failure prior to reoperation . The median survival period following reoperation in this group was only four days . Computed tomography (CT) and/or ultrasonography were performed to localize a source of infection in 24 patients . In nine (82%) of 11 patients, CT identified the abscess, while ultrasonography was positive in 15 (72%) of 21 patients . Neither the interval to operation nor the mortality was significantly different in patients diagnosed with CT and ultrasonography when compared with those who underwent exploration on the basis of clinical findings . To lower the mortality and to shorten the interval to reoperation in these high-risk patients, noninvasive diagnostic testing and confirmation by percutaneous sampling must be sought before the onset of clinical sepsis and organ failure. Scand J Clin Lab Invest, 1987 Jun, 47(4), 355 - 62 Lysosomal enzyme pattern in lung lymph and blood during E . coli sepsis in sheep; Andreasson S et al.; Systemic release of lysosomal enzymes and local release in the pulmonary microcirculation from sequestrated and activated leucocytes could be an important factor in the development of the lung microvascular injury seen after septicaemia . The maximal activities of 11 lysosomal acid hydrolases (acid phosphatase, alpha- and beta-glucosidase, alpha- and beta-galactosidase, alpha-mannosidase, beta-acetylglucosaminidase, beta-glucuronidase, arylamidase and cathepsins B and C) were measured in serum and lung lymph from seven sheep before and after infusion of live E . coli bacteria . In the early phase of septicaemia (the first hour) the activities of eight enzymes were increased in serum and/or lung lymph (1.1 to 2X pre-infusion values) . In the late phase, 3-4 h after sepsis, there were significantly elevated serum activities of beta-glucosidase (5.4X), alpha- and beta-galactosidases (2.7X, 1.5X), beta-acetylglucosaminidase (2.0X) arylamidase (1.2X) and cathespin B (1.7X) . In lymph acid phosphatase (1.7X), alpha- and beta-glucosidases (1.6X, 6.4X), alpha- and beta-galactosidases (2.1X, 1.7X) . Beta-acetylglucosaminidase (2.6X), and beta-glucuronidase (4.0X pre-infusion) were elevated . The findings of a heterogenicity of changes in serum and lymph activities, as well as the large molecular sizes of some of the enzymes with changed activities indicated to us that permeability changes were not major causes of increased lymph enzyme activities . The results could indicate a local release of enzymes either from sequestrated leucocytes or lung tissue due to local reactions in the lung or lung microvessels . The heterogenous changes in activities for the various lysosomal enzymes as found in the present study indicated that measurement of only one enzyme could be misleading.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Sci (Lond), 1987 Jun, 72(6), 683 - 91 Time course of changes in hepatic metabolism in response to sepsis in the rat: impairment of gluconeogenesis and ketogenesis in vitro; de Vasconcelos PR et al.; The time course (12, 24 and 48 h) of changes in blood metabolites, and in gluconeogenesis and ketogenesis, in isolated hepatocytes from rats made septic by caecal ligation and puncture was measured . Blood glucose was not significantly different in septic rats, but lactate was increased at 12, 24 and 48 h; pyruvate and alanine were increased at 48 h . The blood ketone body concentrations were decreased at all times studied after induction of sepsis . These changes were accompanied by increased plasma insulin in the septic rats . The rate of hepatic lipogenesis in vivo was increased at 24 and 48 h . There were appreciable increases in the hepatic concentrations of alanine (200%), lactate (200%) and pyruvate (100%) as well as other intermediates in the gluconeogenic pathway . The hepatic concentrations of acetyl-CoA and ketone bodies were decreased . The rate of gluconeogenesis from added lactate, pyruvate, alanine and glutamine was depressed in isolated hepatocytes from septic rats at 24 and 48 h . The basal rate of ketogenesis or the rate from butyrate in isolated hepatocytes was not significantly altered by sepsis, whereas the rate from oleate was decreased at all time points . It is concluded that there is an impairment of the capacity for gluconeogenesis and ketogenesis in livers of septic rats . The latter may be due to decreased entry of long-chain acyl-CoA into the mitochondria for oxidation . The possibility that these changes are in part brought about by the hyperinsulinaemia associated with the sepsis is discussed. Allergol Immunopathol (Madr), 1987 May-Jun, 15(3), 145 - 9 Complement and sepsis; Gutierrez-Fernandez J et al.; The present study is an evaluation of changes undergone in the serum of factors C3 and C4 of the complement, IgG, IgA, IgM and circulating immune complexes during the initial phase of sepsis and throughout its development in 53 patients, with the object of establishing their prognostic value . During the initial phase of sepsis the determination of the serum levels of immunoglobulins (IgG, IgA, IgM), C3 and C4 complement components and circulating immune complexes lack prognostic interest . Nevertheless, the disappearance of circulating immune complexes, together with an intensive reduction in concentration of IgG, IgM, and C3 and C4 complement components below the range of normality, during the evolutive course, is an indication of a bad prognosis. Pediatr Infect Dis J, 1987 May, 6(5), 443 - 6 Sepsis screen in neonates with evaluation of plasma fibronectin; Gerdes JS et al.; Two hundred twenty neonates with suspected early onset sepsis were prospectively studied to evaluate the ability of a sepsis screen to discriminate infected from noninfected newborn infants . A positive sepsis screen consisted of positive findings in two or more of the following tests: total white blood cell count; immature/total neutrophil ratio; C-reactive protein; micro-erythrocyte sedimentation rate; or plasma fibronectin . For proved sepsis a four-part screen excluding fibronectin yielded a sensitivity of 100%, specificity of 83%, positive predictive value of 27% and negative predictive value of 100% . In contrast the sensitivity of white blood cell count and immature/total neutrophil ratio was only 46% . Adding fibronectin to the four-part screen provided equal sensitivity and negative predictive value but decreased specificity and positive predictive value . While plasma fibronectin may play an important role in the pathogenesis of neonatal sepsis, it is not useful as a marker for infection . The screens did not identify preterm infants with late onset nosocomial sepsis . Although clinical judgment should be the primary factor in the decision to institute antibiotic therapy, a simple four-part sepsis screen provides valuable presumptive information for excluding the diagnosis of early onset neonatal sepsis. Pediatr Infect Dis J, 1987 May, 6(5), 440 - 2 Impaired sensitivity of a single early leukocyte count in screening for neonatal sepsis; Rozycki HJ et al.; The common clinical practice of using a single, early white blood cell (WBC) count to screen for early onset neonatal sepsis was investigated in a population of 61 newborn infants with culture proven sepsis in the first 3 days of life . Thirteen patients (21%) had a falsely normal WBC screening test . The patients with true positive and falsely normal WBC counts did not differ by risk factors for sepsis, birth weight, age, outcome or severity of disease . However, there was a significant delay between the screening test and the positive blood culture in the patients with false normal WBC counts and not in the patients with positive abnormal WBC counts (14.9 +/- 5.9 hours vs . 2.8 +/- 1.4 hr, mean +/- SE, P less than 0.001) . A WBC count obtained soon after birth as currently utilized may not adequately screen for early onset neonatal sepsis. Med Clin North Am, 1987 May, 71(3), 541 - 9 Pharmacologic management of the critically ill patient in the perioperative period--emphasis on the sepsis syndrome; Chernow B et al.; The critically ill perioperative patient requires complex pharmacologic management . The ability to measure circulating drug concentrations has helped the clinician to properly modulate therapy, especially with potentially toxic agents . Postoperative sepsis remains a difficult therapeutic problem . Controversial therapies, such as the use of corticosteroids and the utility of newer pharmacologic approaches, are beginning to be properly tested in multicenter trials . Improvements in technology (e.g., development of monoclonal antibodies), biochemistry, and pharmacology have resulted in the development of exciting, new pharmacologic avenues for the management of the critically ill perioperative patient. Acta Chir Scand, 1987 Apr, 153(4), 261 - 6 Influence of injury and nutrition on muscle water and electrolytes: effect of severe injury, burns and sepsis; Bergstrom JP et al.; The changes in water and electrolyte metabolism associated with severe injury and sepsis are well recognized but changes in tissue content have seldom been available . This report combines the experience obtained from muscle biopsies of such patients performed in two centers; one located in Sweden and one in the U.S . Normal values for muscle water and electrolytes in each center are in close agreement . Needle biopsies of muscle were performed in 45 Swedish patients and 17 U.S . patients at intervals after injury or infection from the second to the thirtieth day . The patients' nutrition varied from brief periods of hypocaloric intake to prolonged high calorie parenteral nutrition with and without amino acids, as well as with and without fat . Prominent changes appeared during the first week and persisted up to 30 days regardless of the associated nutritional intake . These changes included an increased total muscle water, extracellular water, sodium and chloride and a decrease in muscle potassium and magnesium . This study demonstrates a simultaneous expansion of extracellular volume and a loss of intracellular components . This is in contrast to the experiences reported with less severe injury such as elective operation, where a more modest expansion of extracellular volume is seen and which is not associated with any loss of potassium or magnesium . The magnitude and persistence of these changes in muscle tissue deserve further study, both as to mechanism and implications for therapy. J Surg Res, 1987 Apr, 42(4), 377 - 82 Effect of sepsis and starvation on amino acid uptake in skeletal muscle; Warner BW et al.; Sepsis and starvation are catabolic conditions often occurring simultaneously . We recently found that uptake of the nonmetabolized amino acid analog, alpha-aminoisobutyrate (AIB), was reduced in skeletal muscle during sepsis, and data were presented suggesting that this reduction was caused by a factor present in septic plasma . The purpose of the present study was to determine the effect of starvation on amino acid uptake and to investigate possible interactions between sepsis and starvation regarding effects on muscle amino acid uptake . Soleus muscles were removed intact from rats fasted for 0, 24, 48, or 72 hr . Muscles were incubated for 2 hr in Krebs-Henseleit bicarbonate buffer (pH 7.4) and glucose (5 mM) with or without 0.25 ml of septic plasma (total volume 3 ml) . Muscle AIB uptake progressively decreased by approximately 50% during the first 48 hr of starvation, with no further decrease at 72 hr . Addition of septic plasma in vitro reduced AIB uptake in muscles from fed rats and from rats which had been fasted for 24 hr, but did not further reduce uptake after longer periods of starvation . The results suggest that starvation reduces amino acid uptake in skeletal muscle and that the nutritional status of muscle is an important component of the response to the factor(s) in septic plasma capable of inhibiting amino acid uptake. Orthop Rev, 1987 Apr, 16(4), 271 - 86 The role of radiology in orthopaedic sepsis; Sartoris DJ; The concept of needle biopsy of bone--a technique that is performed frequently at the University of California, San Diego--must be considered . Either fluoroscopy or computed tomography can be used to guide the biopsy . The percutaneous approach can eliminate the need for surgery in certain cases in which the orthopaedist would otherwise need to perform an open procedure . A large-bore Craig needle is generally employed, and diagnostic tissue can be obtained, even from difficult sites in most cases . The use of CT in this situation can be helpful, since it documents the exact location of the needle with respect to the affected area (Fig 30). J Appl Physiol, 1987 Apr, 62(4), 1422 - 9 Sepsis in sheep reduces pulmonary microvascular sieving capacity; Smith L et al.; The changes in pulmonary microvascular permeability in sheep, after infusion of live Escherichia coli, were studied using estimations of the osmotic reflection coefficients (sigma) for total protein, albumin, immunoglobins (Ig) G and M and based on these estimations equivalent pore dimensions were calculated . A chronic lung lymph fistula was prepared in seven sheep . After a base-line period, left atrial pressure (Pla) was increased . E . coli (10(9) X kg body wt) were given after attaining filtration independent L/P values . The sigma's for the normal lung were calculated to 0.73 for total protein and to 0.65, 0.76, and 0.91 for albumin, IgG, and IgM, respectively . The equivalent pore radii were determined to 50 and 175 A with 35% of the filtration accounted for by the large pores . After bacterial infusion, the sigma's for total protein, albumin, IgG, and IgM decreased significantly from preseptic values to 0.58, 0.50, 0.64, and 0.83, respectively . After sepsis the small pores were 50 A and the large pores 200 A with 49% of total volume flow at maximum lymph flows occurring through the large pores . Assuming a constant small-pore population the large-pore number increased 32% after bacterial infusion . These results indicate that pulmonary microvascular permeability may have increased due to the sepsis. Scand J Gastroenterol, 1987 Apr, 22(3), 261 - 7 The effect of splenectomy on Escherichia coli sepsis and its treatment with semisoluble aminated glucan; Almdahl SM et al.; Rats were subjected to sham laparotomy or splenectomy and were challenged with either 0.2 X 10(9) Escherichia coli intravenously or 1 X 10(9) E . coli intraperitoneally . By means of quantitative blood culturing asplenic animals were shown to have a significantly impaired ability to clear the bacteria in both forms of challenge . Treatment with intraperitoneally injected semisoluble aminated glucan (SAG), known to have strong macrophage-stimulatory properties, compensated completely for the asplenic state . The substance protected against postsplenectomy sepsis both when given before and when given after removal of the spleen . This protective effect of SAG seemed to last at least 3 weeks. Arch Surg, 1987 Mar, 122(3), 349 - 54 Galactose elimination kinetics in sepsis . Correlations of hepatic blood blow with function; Schirmer WJ et al.; To study hepatic blood flow with clearance techniques during sepsis, it is essential to work within the limitations of the test being applied . Based on galactose elimination kinetics, this study validates galactose clearance at low concentrations as an estimate of effective hepatic blood flow in a rat peritonitis model of cecal ligation and puncture . Hepatic function as determined by galactose elimination capacity fell 25% at ten hours after induction of peritonitis, which correlated closely with the 20% reduction in effective hepatic blood flow at the same time point despite a normal cardiac output . The pattern of reduced flow and reduced function is consistent with intrahepatic flow redistribution . Inadequate flow at the microvascular level with secondary cellular injury may explain the liver dysfunction observed during sepsis. Am J Clin Pathol, 1987 Mar, 87(3), 405 - 7 Primary amyloidosis with diffuse splenic infiltration presenting as fulminant pneumococcal sepsis; Frank JM et al.; This case illustrates a unique clinical presentation of primary systemic amyloidosis, namely, overwhelming pneumococcal sepsis . Although there exists a well-established association between hyposplenism and overwhelming bacterial infection, amyloid replacement of the spleen as a primary cause of the hyposplenism has not been reported . Functional hyposplenism in regard to the effect of the spleen on erythrocytes has been reported in cases of diffuse splenic amyloid infiltration . The patient described had a fulminant course and associated disseminated intravascular coagulation, two clinical features more commonly seen in pneumococcemia occurring in asplenic patients as opposed to patients with normal splenic function . He had no predisposing factors, other than amyloid replacement of the spleen, to account for the development of overwhelming pneumococcemia . The immunologic function of the spleen in protection against overwhelming bacterial infection is briefly discussed. Crit Care Med, 1987 Mar, 15(3), 198 - 203 Dependence of oxygen consumption on cardiac output in sepsis; Wolf YG et al.; We studied the relationship between oxygen consumption (Vo2) and cardiac output in 17 hemodynamically stable, septic and eight nonseptic ICU patients . Each received 300 ml of fresh-frozen plasma or 25% albumin with up to 500 ml of crystalloids, in addition to regular maintenance fluids; this treatment increased pulmonary wedge pressure (WP) by 3 to 4 mm Hg . Measurements were performed before and after approximately 5 h of volume loading . Because cardiac index (CI) decreased as WP increased in four septic and three nonseptic patients, we grouped the data according to the state of flow instead of the recording time sequence . From low to high flows, mean CI increased in septic patients and nonseptic patients . Oxygen delivery (Do2) increased in septic and nonseptic patients . Vo2 remained unchanged in nonseptic patients, while it increased in septic patients . Accordingly, arteriovenous oxygen difference narrowed in nonseptic patients from 4.46 +/- 1.62 to 3.59 +/- 1.21 ml/dl (p less than .05) but did not change in septic patients . In the septic group, the difference in CI between high and low flows was significantly (p less than .05) greater in survivors than in nonsurvivors . We conclude that the septic state is accompanied by a peripheral oxygen deficit, which can be partially reversed by maintaining an above-normal CI and Do2. Pediatrics, 1987 Mar, 79(3), 422 - 5 Buffy coat transfusions in neonates with sepsis and neutrophil storage pool depletion; Wheeler JG et al.; A randomized study was initiated in neonates with neutropenia (absolute peripheral neutrophil count less than 1,500/microL) and suspected bacterial infection . Twenty infants with proven infection were enrolled, nine of whom had depletion of bone marrow stores of maturing neutrophils (less than or equal to 7% metamyelocyte, band and mature forms per 100 nucleated cells) . These nine were randomized to receive 15 mL/kg of either buffy coat transfusions (group 2) or plasma and blood products (group 3) . The remaining 11 (group 1) were observed . Peripheral neutrophil counts were monitored to determine the neutrophil response to transfusions . There were ten of 11 patients in group 1, two of four in group 2, and two of five in group 3 who lived at least seven days . No complications of transfusion were noted . No difference in the rate of peripheral neutrophil increase was found among the three groups . The study was stopped when it became clear that sufficient numbers of patients could not be entered into the study, in a reasonable period of time, to prove or disprove a clinically significant improvement in outcome . Although in vitro testing of the buffy coat preparations showed normal function in three of four cases, the clinical quality of the buffy coats may have been inadequate because of poor availability of whole fresh blood less than 24 hours old . The role of neutrophil transfusions in these patients remains unclear. Surgery, 1987 Feb, 101(2), 213 - 6 A ten-year review of Candida sepsis and mortality in burn patients; Prasad JK et al.; A retrospective analysis of Candida sepsis was carried out in 1722 burn patients admitted to this center from 1975 to 1984 . Cultures were positive for Candida in 233 (13.5%) of these patients during their hospitalization . Candidemia was present in 70 (4.0%) of the 1722 patients . Of the 70 patients with candidemia, 38 (54%) died . However, only 11 patients (15.7%) died of Candida sepsis or mixed Candida and bacterial sepsis (less than 1% of the total patient population) . The remaining 27 patients who had candidemia died of bacterial septicemia or organ system failure . The low incidence of Candida and the low incidence of mortality due to Candida was attributed to a comprehensive program of prevention, detection, and treatment . Early initiation of treatment with amphotericin B was an important aspect of the program. Clin Pharm, 1987 Feb, 6(2), 154 - 9 Decreased hepatic clearance of clindamycin in critically ill patients with sepsis; Mann HJ et al.; Clindamycin pharmacokinetics was compared in critically ill patients with sepsis and healthy volunteers, and the relationship between pharmacokinetic values and physiological measurements obtained from the critically ill patients was characterized . Pharmacokinetic evaluations were performed on 10 patients with sepsis who were receiving clindamycin phosphate 900 mg i.v . every eight hours and on 6 previously studied healthy men receiving the same dosage regimen . Physiological variables measured included age, weight, cardiac index, systemic vascular resistance, central venous pressure, liver-function tests, alpha 1-acid glycoprotein concentration, and APACHE II score . Clindamycin was administered to the critically ill patients via a central venous catheter over 30 minutes; the healthy volunteers received their infusions via a peripheral venous catheter over 30 minutes . Blood samples were obtained at five minutes before and at various intervals after drug administration . Serum clindamycin concentrations were determined by a gas-liquid chromatographic method . Serum concentration data were analyzed using noncompartmental methods based on statistical moment theory, and the a priori level of significance was 0.05 . The critically ill patients had significantly increased values for area under the curve (AUC), area under the moment curve (AUMC), mean residence time (MRT), and average concentration at steady state (Css), while total body clearance (TBC) was less than half that in the healthy volunteers . TBC in three of the critically ill patients was not different from that in the healthy volunteers . The apparent volume of distribution at steady state (Vss) was not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Pharm, 1987 Feb, 6(2), 148 - 53 Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis; Mann HJ et al.; The pharmacokinetic disposition of aminoglycosides in critically ill patients with sepsis was studied . In an open-label study of the disposition of gentamicin and tobramycin, individualized pharmacokinetic values of 100 critically ill patients in the surgical intensive-care unit were compared with those of a concurrently monitored group of 100 surgery patients who were not critically ill . The a priori computer-predicted dosage requirements of the critically ill patients were also compared with the dosages derived from their individualized pharmacokinetic values, and intrapatient variation in the critically ill patients was studied . Serum concentration-time data were analyzed using a one-compartment model and the DataMed Clinical Support Services system to provide individualized dosage requirements . Initial dosing guidelines were also generated for the critically ill patients using the a priori model of the DataMed Clinical Support Services program and patient demographic information . The critically ill patients were significantly older, had higher serum creatinine concentrations (SCr), and had lower elimination rate constants (k) and total body clearances (CL) than the surgery patients who were not critically ill . The volume of distribution (V) was not significantly different . The a priori computer predictions for the critically ill patients were significantly lower than the individualized values for V, CL, dose, and amount of drug per 24 hours . The dosing regimen from the a priori model was the same as the individualized regimen in only 2/100 patients . In the 76 critically ill patients who had a second pharmacokinetic analysis performed, there was a significant decrease in k and CL from the first analysis.(ABSTRACT TRUNCATED AT 250 WORDS) Arch Surg, 1987 Feb, 122(2), 141 - 6 Sepsis score and acute-phase protein response as predictors of outcome in septic surgical patients; Dominioni L et al.; In a series of 135 patients with severe surgical infections, we determined the sepsis score and the plasma level of the acute-phase proteins alpha-1-acid glycoprotein, alpha 1-antitrypsin, complement factor B, and C3 . The initial sepsis score was a strong determinant of survival: in survivors it was significantly lower than in nonsurvivors . Only 8% of patients with a sepsis score above 20 survived . At the onset of severe sepsis, the plasma levels of all four acute-phase proteins were significantly lower in nonsurvivors . A significant elevation of C3a levels in the plasma of both surviving and nonsurviving patients indicated marked consumption of complement components in all patients with severe sepsis . A linear equation was developed to predict survival: sepsis index of survival (SIS) % = 121 + 0.26 (complement factor B) + 0.36 (alpha-1-acid glycoprotein)-6 (sepsis score) . Based on our analysis, at the onset of severe sepsis, an SIS of 50% or more can correctly predict 88% of survivors and an SIS less than 50% can correctly predict 86% of nonsurvivors several days in advance of clinical outcome. Otolaryngol Head Neck Surg, 1987 Feb, 96(2), 165 - 71 A predictive model for wound sepsis in oncologic surgery of the head and neck; Cole RR et al.; A prospective analysis of patients undergoing surgical resection of squamous cell carcinoma of the upper aerodigestive tract was performed in order to identify the patients at risk of postoperative wound infection and to develop a model predictive of wound infection . Fifty-nine patients who underwent extirpative clean-contaminated procedures--all of whom received cefazolin as the sole chemoprophylactic agent, were studied over a 1-year period . Twenty-three variables were recorded for each patient in the study . The overall rate of wound infection was 25.4% . Univariate analysis indicated that three variables were significantly related to the likelihood of postoperative wound infection . These included tumor stage (P = 0.0180), nodal stage (P = 0.0062), and duration of surgery (P = 0.0151) . The Biomedical Computer Program (BMDP), a logistic regression program specifically designed for a binary dependent variable (infection vs . no infection) based on independent variables that may be continuous or categorical, was used in development of a model predictive of wound infection . T-stage, N-stage, and the presence of concomitant disease made up the combination of factors found to be most predictive of infection in our study population . Considering "success" to be the development of infection if the probability was 75% or higher, and the absence of infection if the probability was less than 25%, the multiple regression analysis model demonstrated a predictive success rate of 74.6% . Our results indicate that the risk of infection in patients undergoing clean-contaminated oncologic surgery of the head and neck is greatest for patients who have advanced disease that requires prolonged surgery in the presence of concomitant diseases.(ABSTRACT TRUNCATED AT 250 WORDS) J Trauma, 1987 Jan, 27(1), 52 - 7 Chronic sepsis following intramedullary nailing of femoral fractures; Green SA et al.; We reviewed 12 patients with chronic drainage after intramedullary nailing of a femoral shaft fracture . The fractures tended to be the result of high-speed trauma and were frequently comminuted . Six were open fractures and six were closed injuries . All but one had been managed initially with the open nailing technique, exposing the fracture site . In six cases we left the nail in place until bone union occurred, an average of 33 months after injury, removing the hardware thereafter . The remaining six patients, each with bone sequestra at the fracture site, underwent nail removal, debridement of nonviable bone, and external fixation followed by bone grafting; this group took 37 months to heal . There was one persistent nonunion in each group . Drainage did not cease in either group until the nail and all sequestra had been removed . There was an average of 4.3 cm of shortening, but no angulation greater than 10 degrees . Six patients were left with less than 45 degrees of knee flexion and only five had 100 degrees or more of knee flexion. Arch Surg, 1987 Jan, 122(1), 78 - 81 Supplemental dietary tyrosine in sepsis and acute hemorrhagic shock; Simon R et al.; Previous studies showed that dopamine and norepinephrine levels in rat brain are reduced following stress and that rats fed supplemental tyrosine do not exhibit these reductions . We hypothesized that dietary supplementation with tyrosine would enhance resistance to acute hemorrhagic shock and sepsis by increasing substrate (tyrosine) availability for catecholamine synthesis . Rats were fed either a standard rat chow (6.8 g of tyrosine per kilogram of chow), which supports normal growth, fertility, and longevity, or the same chow supplemented with 10 g of tyrosine per kilogram of chow . Seven days later, the rats underwent cecal ligation and perforation while under intraperitoneal pentobarbital anesthesia . There was a significant increase in survival in the tyrosine-supplemented group . Similarly, in another experiment, tyrosine-supplemented rats were able to tolerate acute fulminant hemorrhagic shock better than were nonsupplemented control animals. Arch Surg, 1987 Jan, 122(1), 62 - 8 Hemorrhage without tissue trauma produces immunosuppression and enhances susceptibility to sepsis; Stephan RN et al.; To determine whether hemorrhage without major tissue trauma can itself produce immunosuppression, the effect of hemorrhage on the lymphocyte response to T-cell mitogen in endotoxin-resistant C3H/HEJ mice was measured . The mice were bled to achieve a mean blood pressure of 35 mm Hg, maintained at that level for one hour, and then adequately resuscitated . On days 1 through 10 thereafter, the proliferative responses of the splenocytes to concanavalin A were measured and allogeneic mixed lymphocyte reaction was performed . The proliferative responses to mitogen stimulation as well as the results of mixed lymphocyte reaction studies indicated that marked immunosuppression occurred at day 1 . Immunosuppression persisted for at least five days following hemorrhage, as evidenced by mitogen stimulation assay . Another group of mice was subjected to sepsis three days after hemorrhage and resuscitation . The mortalities in the sham-hemorrhage and hemorrhage groups following sepsis were 58% and 100%, respectively . Thus, a significant depression of cellular immunity occurred following simple hemorrhage despite adequate resuscitation, and this immunosuppression enhanced the susceptibility to sepsis. Pancreas, 1987, 2(5), 499 - 505 Sepsis indicators in acute pancreatitis; Block S et al.; Twenty-one routine clinical and laboratory data in 161 patients with necrotizing pancreatitis (NP) undergoing surgical treatment were analyzed . The necrotic tissue at operation was bacterially infected in 41% of the patients . The goal of the study was to evaluate whether there was any special clinical feature in cases of an infection . The parameters were recorded during 48 h after admission as well as during 48 h before operation, and the frequencies submitted to both a univariate and a multivariate analysis (logistic regression model) . In the period after admission, patients with infected necrosis significantly more often had a rectal temperature greater than 38.5 degrees C (p = 0.001) . Before operation (i.e., after maximum conservative treatment), four findings were significantly related to an infection: rectal temperature greater than 38.5 degrees C, base excess greater than -4 mmol/L, hematocrit less than 35% (all p = 0.0001), and paO2 less than 60 mm Hg (p = 0.001) . The multivariate analysis, which calculates and quantifies the mutual influence of factors, showed a combination of three findings (rectal temperature greater than 38.5 degrees C, base excess greater than -4 mmol/L, and hematocrit less than 35%) to be related to necrosis infection before operation . All three criteria in a patient imply a probability of infection of 83% . It is noteworthy that the sepsis indicators were equally distributed in patients with focal, extended, or subtotal/total infected necrosis, but correlated with the necrosis extent in sterile necrotizing pancreatitis . Moreover, all parameters not related to the pancreatic infection {e.g., hyperglycemia, hypocalcemia, rise of lactic dehydrogenase (LDH), and the white blood cell count} correlated with the three necrosis categories. Circ Shock, 1987, 22(1), 1 - 9 Alterations in hepatic membrane potentials in vivo during early and late sepsis; Clemens MG et al.; To determine whether alterations in hepatocyte membrane electrical responses might play a role in glucose dyshomeostasis during sepsis, hepatocyte membrane potentials were measured in vivo in rats made septic by cecal ligation and puncture (CLP) . In both early-septic (8-10 hr after CLP) and late-septic (18-20 hr after CLP) rats, resting hepatocyte membrane potentials were significantly depressed compared to those in sham-operated rats . In addition, the hyperpolarization response to glucagon administration in vivo which was observed in the sham-operated rats was significantly attenuated in both early- and late-sepsis rats . To determine whether this blunted hyperpolarization response was related to defects in stimulation of gluconeogenesis, livers from sham-operated and early-sepsis rats were isolated and perfused . The livers from sham-operated rats responded to 1 nM glucagon by increasing glucose release by 53%, while those from septic rats increased by only 20% . These results suggest that a defect associated with the plasma membrane may be an early event in the development of glucose dyshomeostasis during sepsis. Circ Shock, 1987, 22(2), 185 - 93 Pulmonary microvascular changes during hyperdynamic sepsis in an ovine model; Traber DL et al.; Hyperdynamic sepsis (increased cardiac output and reduced peripheral vascular resistance) was created in sheep with chronic lung lymph fistulae (n = 8) by giving them a 30-min infusion of 1.5 micrograms/kg of endotoxin (LPS) iv . Four hours after LPS the cardiac output (CO) was reduced (6.56 +/- 0.43 to 4.96 +/- 0.33 liters/min) and lymph flow was increased (5.4 +/- 1.0 to 18.6 +/- 3.1 ml/h) . Nine hours after LPS the CO output was increased (8.42 +/- 0.60 liters/min) . Early cardiopulmonary changes were associated with a fall in neutrophils (PMNs) (2,667 +/- 748 to 450 +/- 90 cells/microliter) and an elevation of their chemiluminescence (CL), an indication of increased O2 free-radical formation in the blood (1,250 +/- 160 to 3,340 +/- 744 units/1,000 leukocytes) . The granulocytic enzyme, aryl sulfatase, was increased in the lymph (0.19 +/- 0.03 to 0.37 +/- 0.05 microgram/h/mg protein) indicating degranulation (activation) of PMNs . When CO was increased (9 h after LPS), blood CL rose even higher (5,330 +/- 173 units/1,000 leukocytes) and CL in the lung lymph decreased (1,160 +/- 220 units/1,000 leukocytes) . At this time, lymphatic aryl sulfatase had returned to baseline levels (0.25 +/- 0.02 microgram/h/mg protein) . These data suggest that pulmonary microcirculatory injury produced by LPS may be the result of margination of PMNs in the lung and their release of permeability-inducing mediators . Later, as the CO increases, the PMNs or their lesion-producing mediators may be washed from the lung and the lung injury thus may be made less severe. Circ Shock, 1987, 21(4), 253 - 9 Imidazole and indomethacin improve hepatic perfusion in sepsis; Schirmer WJ et al.; Visceral microcirculatory insufficiency has been demonstrated in sepsis despite a hyperdynamic systemic circulation . This study examines the effect of the cyclo-oxygenase inhibitor indomethacin and the thromboxane synthetase inhibitor imidazole on septic hemodynamics and visceral perfusion in a septic rat model of cecal ligation and puncture . Animals received either indomethacin (INDO), imidazole (IMID), or saline intramuscularly at t = 0, 6, and 12 hr of peritonitis . Thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, effective hepatic blood flow, effective renal plasma flow, and arterial and mixed venous blood gases were determined at 15 hr . Both INDO and IMID improved effective hepatic blood flow in the septic animals to virtually sham, nonseptic levels without significantly altering systemic hemodynamics . This study suggests that the reduction in hepatic perfusion in sepsis may be mediated by thromboxane, the synthesis of which is suppressed by both INDO and IMID. Aust N Z J Surg, 1987 Jan, 57(1), 41 - 7 Energy and protein metabolism in sepsis and trauma; Shaw JH et al.; Energy and protein metabolism in septic and trauma patients has been extensively studied over the past 30 years . Despite this, a number of inconsistencies are present in the literature and it is difficult to formulate a clear global picture of this complex series of metabolic events . Conclusions from human studies have often been hampered by the utilization of small numbers of patients, and data from animal models of sepsis or trauma are often difficult to interpret . Over the past 5 years, the authors have performed a series of isotopic infusions in normal volunteers, and in patients with either sepsis or trauma, in order to gain a clearer understanding of energy and protein metabolism in severely stressed patients . This review summarizes the findings. Arch Surg, 1987 Jan, 122(1), 26 - 32 Complement-mediated neutrophil activation in sepsis- and trauma-related adult respiratory distress syndrome . Clarification with radioaerosol lung scans; Tennenberg SD et al.; Complement-mediated neutrophil activation (CMNA) has been proposed as an important pathogenic mechanism causing acute microvascular lung injury in the adult respiratory distress syndrome (ARDS) . To clarify the relationship between CMNA and evolving lung injury, we studied 26 patients with multiple trauma and sepsis within 24 hours of risk establishment for ARDS . Pulmonary alveolar-capillary permeability (PACP) was quantified as the clearance rate of a particulate radioaerosol . Seventeen patients (65%) had increased PACP (six developed ARDS) while nine (35%) had normal PACP (none developed ARDS; clearance rates of 3.4%/min and 1.5%/min, respectively) . These patients, regardless of evidence of early lung injury, had elevated plasma C3adesArg levels and neutrophil chemotactic desensitization to C5a/C5adesArg . Plasma C3adesArg levels correlated weakly, but significantly, with PACP . Thus, CMNA may be a necessary, but not a sufficient, pathogenic mechanism in the evolution of ARDS. Indian J Ophthalmol, 1987, 35(5-6), 143 - 5 Keratomycosis in corneal sepsis; Sharma SL et al.; 510 cases of corneal ulceration were studied for the presence of fungus as a causative organism . Fungus was found in 87 (17.5%) most common fungus found was aspergillus . Mucor was found in 16 cases (18.1%) which is higher than earlier reports . History of trauma specially with vegetative matter and the application of steriods for one purpose or the other is a factor of importance as noted in this study. J Am Acad Dermatol, 1987 Jan, 16(1 Pt 2), 260 - 3 Fusarium as a pathogen . A case report of Fusarium sepsis and review of the literature; Veglia KS et al.; Fusarium species are known to the dermatologist as cutaneous contaminants . Rarely they occur as pathogens . We report a case of disseminated Fusarium moniliforme in a 44-year-old patient with acute lymphocytic leukemia . We also review the previous reports of human Fusarium infections . The mycologic characteristics of Fusarium, including its nosologic and morphologic characteristics and its response to medications, are discussed. Biochem Soc Symp, 1987, 54, 145 - 62 The role of the citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns; Newsholme EA et al.; Many aspects of the cell biology of lymphocytes and macrophages have been studied extensively over many years . Our recent work on these cells has investigated the fuels utilized, the metabolism carried out and the importance of this metabolism for the specific function of these cells in the immune system . The quantitatively important role of glutamine and the observation that both glutamine and glucose are only partially oxidized by both types of cell have been established . This work has led to a new hypothesis to explain the high rates of partial oxidation of both fuels in lymphocytes and macrophages, and in other cells such as enterocytes, colonocytes and also in neoplastic cells . In addition, the high rate of glutamine utilization and its importance in such cells has raised the question as to the source of this glutamine in the body: the evidence suggests that this is muscle . The metabolic relationship between the glutamine-producing tissue and the cells of the immune system provides an explanation for some well-established changes in metabolism during the condition of surgery, trauma, sepsis and burns . Knowledge of the metabolism of glucose, glutamine, pyruvate and long-chain fatty acids by these cells raises some intriguing questions concerning the role and function of the citric acid cycle in these and other similar cells, including tumour cells. Acta Anaesthesiol Belg, 1987, 38(4), 275 - 9 The disposal of intravenous glucose studied using glucose and insulin clamp techniques in sepsis and trauma in man; Little RA et al.; Whole body glucose uptake and oxidation during a hyperglycemic clamp have been shown to be depressed in hypermetabolic septic patients compared to control subjects despite similar plasma insulin concentrations . Forearm glucose uptake was similarly impaired . Metabolic rate was not increased further by the glucose infusion in the patients although a 20% rise was elicited in the controls . This resistance to the effects of insulin was also clearly demonstrated in trauma patients using the euglycemic clamp technique . The maximal rate of glucose disposal after injury was half that found in controls and the pattern of response was consistent with the insulin resistance being a post-receptor defect. Circ Shock, 1987, 22(1), 73 - 81 Systemic and regional hemodynamic changes after intraperitoneal endotoxin in rabbits: development of a new model of the clinical syndrome of hyperdynamic sepsis; Fink MP et al.; Rabbits were injected intraperitoneally with sterile saline or Escherichia coli endotoxin (LPS; 50 or 500 micrograms/kg) . Sixteen to 18 h later, the animals were anesthetized with ketamine and instrumented to permit measurement of mean arterial pressure, cardiac output (by thermodilution), and regional blood flow (using radioactive microspheres) . The animals were allowed to waken fully in a plastic restraining cage prior to measuring systemic and regional hemodynamics . LPS had similar effects regardless of dose, and results from the two dosage groups have been combined . Compared to controls, administrations of LPS resulted in a 29.3% increase in cardiac output (P = .011) and a 22.8% decrease in systemic vascular resistance (P = .0009) . Injection of LPS caused significant changes in blood flow to the heart (55.3% increase), small intestine (128.3% increase), portal vein (54.7% increase), and hepatic artery (65.0% decrease) . The percentage of cardiac output perfusing the kidneys and hepatic artery was significantly decreased in the endotoxemic group (P = .037 and P = .002, respectively) . Injecting LPS resulted in increased relative flow to the heart (P = .024), small intestine (P = .049), and portal vein (P = .041) . We conclude that this model reproduces several of the systemic hemodynamic features of the sepsis syndrome in humans . In this model, the hyperdynamic state is associated with vasodilatation in mesenteric (small intestine and colon) and coronary beds and vasoconstriction in the hepatic artery. Int J Clin Pharmacol Res, 1987, 7(3), 229 - 31 Cefotetan in the treatment of serious intra-abdominal sepsis: a controlled clinical trial; Scott SD et al.; Cefotetan has been compared with two regimens of combination antibiotic therapy in the treatment of peritonitis and serious intra-abdominal sepsis . One hundred predominantly elderly patients (median age 66 years) were entered into a prospective randomized surgical trial . Sixty-two per cent had peritonitis . There were seven non-septic deaths . Side-effects were similar in each group and generally of a minor, self limiting nature . Haematological and biochemical factors were closely monitored, and though there were increases in the prothrombin time, there was no statistical difference between cefotetan and comparators . Cefotetan is as effective as combination therapy in the treatment of surgical patients with serious intra-abdominal sepsis. Prog Clin Biol Res, 1987, 236B, 85 - 95 Can the outcome after trauma or sepsis be predicted from biochemical or hormonal parameters? Pasch T, Mahlstedt J, Pichl J, Buheitel G, Pscheidl E. The severity of shock of 36 surgical ICU patients was classified using the Injury Severity Score (N = 20) and the Sepsis Score (N = 16) . A great number of laboratory parameters were repeatedly determined on 5 days following the trauma or the onset of septic symptoms . Blood lactate, C-peptide, BUN, osmolality, and thyroid hormones were most closely related to the severity of the disease . This correlation was, however, less pronounced in the trauma than in the septic patients . Lactate and thyroid hormones showed a typical course in the non-survivors and may therefore be valuable as prognostic indices. Circ Shock, 1987, 22(2), 105 - 13 Inhibition of eicosanoid production by BW755C does not attenuate sepsis-induced alterations in glucose kinetics; Lang CH et al.; Previous studies have indicated that various arachidonic acid metabolites are involved in the cardiovascular dysfunction seen during endotoxemia and sepsis . However, the possible role of these metabolites in mediating the metabolic alterations under similar conditions remains to be elucidated . Thus, the purpose of the present study was to determine if cyclooxygenase and lipoxygenase blockade could prevent the elevated rates of glucose appearance (Ra), glucose recycling, and hyperlactacidemia seen during hypermetabolic sepsis . Sepsis was induced in chronically catheterized conscious rats by multiple injections of live Escherichia coli via a subcutaneous catheter . Septic animals received intravenous (i.v.) injections of BW755C every 6-8 h to block both the cyclooxygenase and lipoxygenase pathways . Glucose kinetics were assessed in 24-h fasted rats by using a constant i.v . infusion of {6-3H} and {U-14C}-glucose . Treatment with BW755C prevented the 1-2 degrees C increase in body temperature induced by sepsis in the vehicle-treated animals . Septic rats receiving saline instead of BW755C exhibited an elevated plasma lactate concentration and increased rates of glucose appearance, recycling, and metabolic clearance . The sepsis-induced alterations in these variables were not attenuated by BW755C . These results suggest that neither arachidonic acid metabolites nor elevated body temperature are responsible for increasing glucose production and utilization in hypermetabolic septic rats. Clin Exp Hypertens A, 1987, 9(8-9), 1493 - 504 Renin-angiotensin system in sepsis; Hilgenfeldt U et al.; The time course of the components of the renin-angiotensin system was investigated in the plasma of three patients on the intensive care unit . Two of them, which were both polytraumatized, suffered from adult respiratory distress syndrome (ARDS) . All patients had sepsis and impaired pulmonary and renal function . Plasma samples were investigated for up to two weeks, in which time all three patients showed a decrease in their angiotensin converting enzyme (ACE) plasma concentration . Two of the patients with deteriorating renal function had three to four times elevated angiotensinogen (Ao) plasma levels, which were measured by both the direct and indirect radioimmunoassay . The ratio of the mean values between both assays was 1:1 in two patients and shifted to higher values in the direct assay in the third patient . This suggests that higher amounts of des-AngI-angiotensinogen were present in the latter patient, because "inactive" Ao is also detected by the direct assay . The decrease in active Ao may be caused by an up to twenty times elevated plasma renin activity (PRA) . The PRA was correlated with the angiotensin I (AngI) plasma levels . However, at PRA values higher than 200 pmol AngI/ml/h this correlation decreased because of the rapid substrate consumption . In addition there was a good correlation between AngI and AngII plasma levels in two patients which could not be observed in the patient with the highest PRA and AngII values . A relationship between plasma ACE concentration and AngII formation could not be observed . Thus in two of the three septic patients the components of the renin angiotensin system were extremely stimulated at very low blood pressure values . These data show, that it is reasonable to follow the time course of the components of the renin angiotensin system in single patients . In addition it is demonstrated that the direct measurement of Ao is a valid supplement in the diagnosis of the renin angiotensin system. Metabolism, 1987 Jan, 36(1), 14 - 20 Alterations in metabolite levels in carbohydrate and energy metabolism of rat in hemorrhagic shock and sepsis; Mori E et al.; For comparison of the extent of metabolite content alteration caused by etiologically different types of shock, septic peritonitis and hemorrhagic shock (mean arterial blood pressure at 40 mm Hg for 1 h or 2 h) were produced in rats . Contents of metabolites were determined in the liver and the muscle . Characteristic differences were found in the alteration modes of hepatic lactate level, muscle adenine nucleotide concentrations, and muscle protein content between these shock models . Rapid and significant alterations were observed in the levels of adenine nucleotides, glucose-6-phosphate and lactate in the liver in both types of shock . Hepatic energy charge and contents of glycogen and protein also significantly decreased . On the other hand, noticeable changes in the muscles were elevation of lactate level and the decrease of phosphocreatine and protein concentrations . Another distinct change was the decrease of total adenine nucleotide content in the muscle of septic rats, whereas it remained unchanged in the muscle of hemorrhagic shock rats . Thus, the changes of metabolite levels did not occur simultaneously in different tissues, and their rate and magnitude varied between different types of shock . The difference in adaptive response of metabolism may result in pathophysiologic diversity in shock. Br J Surg, 1986 Dec, 73(12), 958 - 60 Combined topical povidone-iodine and systemic antibiotics in postappendicectomy wound sepsis; Lau WY et al.; Three hundred and fifteen patients with appendicitis were randomized into two groups . One group received pre-operative systemic gentamicin and metronidazole while the other group received 1 per cent topical povidone-iodine solution in addition to the antibiotics . For early appendicitis including normal and acutely inflamed appendices, only one dose of antibiotics was used . The postoperative wound sepsis was very low in both groups of patients and there was no statistical difference between them . For late appendicitis including gangrenous and perforated appendices, the antibiotics were continued for 7 days . Eight out of 51 patients who had the topical agent developed wound sepsis compared with one out of 52 patients who received no topical agent . This difference is statistically significant (P = 0.03) . All wound infections presented within 2 weeks of operation and were deep . Povidone-iodine, 1 per cent, adversely affects the wound infection rate in late appendicitis and should not be used. Acta Chir Scand, 1986 Dec, 152, 721 - 6 Plasma fibronectin concentration in suspected septicaemia is related to severity of sepsis; Brodin B et al.; Low plasma fibronectin levels have been reported in patients with septic complications following surgery, major trauma or burn injury . Our purpose was to evaluate fibronectin in suspected septicaemia and its relationship to severity of infection and clinical outcome . In 51 consecutive patients with infection classified as mild (group A), severe (group B) or severe complicated by septic shock, disseminated intravascular coagulation or multiple organ failure (group C), the respective mean initial fibronectin concentrations were 85% +/- 10 (SD), 55% +/- 15 and 44% +/- 13 of the reference mean (0.35 g/l) . In statistical analysis the groups differed significantly from each other and from controls . All 11 patients with mild infection had fibronectin values above the lower reference limit, which was 60%, whereas in 15 of 16 group C patients and all seven fatal cases in that group the initial fibronectin values were below 60% . Plasma fibronectin rose with clinical improvement, but remained low in patients with persisting septicaemia . The results confirmed earlier reports of low fibronectin levels in septic states, and indicate that low concentration is of prognostic value and is related to the severity of the disease. J Antimicrob Chemother, 1986 Nov, 18(5), 613 - 9 Cefoxitin versus gentamicin and metronidazole in prevention of post-appendicectomy sepsis: a randomized, prospective trial; Lau WY et al.; Three hundred and seven patients with appendicitis were randomized to receive cefoxitin or gentamicin and metronidazole . For early appendicitis, a single preoperative dose of antibiotics was given . For late cases, the antibiotics were continued postoperatively for seven days . Both cefoxitin and gentamicin-metronidazole were effective in the reduction of post-appendicectomy septic complications in early or late appendicitis and there was no statistically significant difference between them . Mild transient and reversible nephrotoxicity was detected in 1.9% of patients who received gentamicin-metronidazole for seven days . Nephrotoxicity was not detected in any other patients . The cost of cefoxitin is higher, but this has to be balanced against the costs of monitoring serum gentamicin and creatinine levels, and the need to adjust the gentamicin dosage in 19% of patients when gentamicin-metronidazole was used . Both cefoxitin and gentamicin-metronidazole are effective and safe when used carefully . Cefoxitin has a slight advantage in its lack of potential nephrotoxicity and ototoxicity. Am Rev Respir Dis, 1986 Nov, 134(5), 873 - 8 The effect of fluid loading, blood transfusion, and catecholamine infusion on oxygen delivery and consumption in patients with sepsis; Gilbert EM et al.; Fifty-four patients with systemic sepsis and signs of circulatory shock were prospectively investigated immediately before and after 1 of 3 therapeutic interventions chosen to increase systemic oxygen delivery (DO2): colloidal fluid loading (Group I, n = 20), blood transfusion (Group II, n = 17), or catecholamine infusion (dopamine or dobutamine, Group III, n = 17) . Patients in Groups I and II with normal blood lactate concentrations (less than 2.2 mmol/L) exhibited no significant increases in systemic oxygen consumption (VO2) in response to the increases in DO2 . However, significant increases in VO2 were noted in patients in Groups I and II with elevated lactate concentrations (greater than 2.2 mmol/L) . In contrast to patients in Groups I and II, patients in Group III with and without lactic acidosis exhibited significant increases in VO2 after catecholamine administration . Lactic acidosis, a clinical marker of anaerobic metabolism or oxygen debt, appears to predict increases in VO2 in response to increases in DO2 in septic patients receiving fluid and catecholamines increase VO2 without regard for the presence or absence of anaerobic metabolism . The results of this clinical trial therefore suggest that catecholamines may exert a direct effect on oxidative metabolism. Emerg Med Clin North Am, 1986 Nov, 4(4), 809 - 40 Sepsis and septic shock; Ellrodt AG; Sepsis and septic shock remain all too frequent syndromes in modern medicine with unacceptably high mortality rates . Physicians must be aware of the many ways in which sepsis and septic shock may present and the multiple differential diagnoses . Early recognition and prompt institution of empiric therapy are of utmost importance . Our current limited understanding of the pathophysiology of sepsis and septic shock significantly limits our ability to treat this syndrome effectively and thus substantively alter mortality . New developments in immunology and metabolism seem promising in furthering our understanding and improving our therapy of this complex multisystem disorder. Am J Physiol, 1986 Nov, 251(5 Pt 2), R984 - 95 Rat liver free cytosolic Ca2+ and glycogen phosphorylase in endotoxicosis and sepsis; Deaciuc IV et al.; Rats were treated with Escherichia coli endotoxin (ET) either acutely or chronically or rendered septic by cecal ligation and puncture . At 6 h after ET injection, at various intervals of continuous ET infusion, and at 17-18 h after the onset of peritonitis, animals were killed and hepatocytes were isolated . Cytosolic {Ca2+} ({Ca2+}c) was measured by quin 2 during the resting state and after stimulation with epinephrine and vasopressin . Basal and epinephrine-, vasopressin- and glucagon-stimulated glycogen phosphorylase activity were also determined . In hepatocytes from acutely ET-treated rats, resting levels of {Ca2+}c were decreased 46% from 245.8 +/- 11.0 to 131.0 +/- 8.5 nM (n = 4-6, P less than 0.05) . In septic rats a 39.5% decrease was noted {i.e., from 154.0 +/- 17.7 (n = 4, sham) to 93.3 +/- 91 nM (n = 5, septic, P less than 0.05)} . These decreased {Ca2+}c levels were associated with changes of glycogen phosphorylase activity in a manner suggesting a cause and effect relationship; e.g., acute ET treatment resulted in greater than 80% depression of phosphorylase a activity, whereas sepsis induced a 58% decrease in the activity of this enzyme . In ET-infused rats the resting level of {Ca2+}c and its response to hormonal stimulation were not different from hepatocytes of saline-infused rats, although glycogen phosphorylase activity was less responsive to these hormones . The effect on the enzyme's response to Ca2+-mobilizing hormones was more marked than to glucagon . This is consistent with the concept that information flow in the Ca2+-messenger system is a site of metabolic lesions produced by endotoxicosis and sepsis. J Burn Care Rehabil, 1986 Nov-Dec, 7(6), 488 - 91 Fungal sepsis: an increasing problem in major thermal injuries; Pensler JM et al.; In major thermal burns there has been an alarming emergence of fungal sepsis as defined by involvement of three or more organs and/or repeated positive blood cultures . During an 18-month period, we treated 72 patients (aged 18 +/- 2 years; TBSA burn, 57 +/- 3%; percent of third-degree burn, 45 +/- 3) with fungal sepsis . In all patients with documented three-organ involvement, treatment was with intravenous amphotericin (0.5 mg/kg body weight/day), immediate wound debridement, and early wound closure . The mortality was 32% (23 patients); 49 (68%) survived infection . Sixty-two variables were reviewed retrospectively using multiple regression analysis to ascertain specific factors associated with fungal sepsis and their relationship to survival . In burn patients, fungal sepsis is a strong determinant of survival, and its occurrence overshadows traditional factors presently utilized to predict clinical outcome. Pediatr Infect Dis, 1986 Nov-Dec, 5(6), 622 - 5 Intravenous immunoglobulin for prevention of sepsis in preterm and low birth weight infants; Haque KN et al.; The effect of an intravenous polyvalent immunoglobulin preparation given prophylactically to prevent neonatal sepsis was tested in preterm and low birth weight infants . Infants matched for gestational age, sex and birth weight (+/- 250 g) were randomly allocated into 3 groups of 50 each, one group (Group C) being used as control . Group A received Intraglobulin (Biotest Pharma, West Germany), 120 mg/kg intravenously, within 2 to 4 hours of delivery; Group B received the same on days 1 and 8 . The control group received no immunoglobulin . The frequency of infection and serum immunoglobulin concentrations were determined in each group . Infection rate in the control group was 16% (8 of 50) while in each of the treated groups it was 4% (2 of 50) (P less than 0.005) . The immunoglobulin concentrations achieved in the treated group were significantly higher than the control group . No adverse effect of the therapy was noted during the study and at a 6-month follow-up . It is suggested that in nurseries where the infection rate is high, prophylactic intravenous polyvalent immunoglobulin therapy for the preterm and low birth weight infants may provide protection from infection. JPEN J Parenter Enteral Nutr, 1986 Nov-Dec, 10(6), 642 - 5 Total parenteral nutrition catheter sepsis: impact of the team approach; Faubion WC et al.; For a period of 32 months from the inception of the Parenteral and Enteral Nutrition (PEN) Team at the University of Michigan, the infection rate (IR) related to central venous catheters (CVCs) for total parenteral nutrition (TPN) was prospectively evaluated . Six hundred twenty-two catheters were placed in 377 patients for a total of 9,200 patient days . The length of CVC stay ranged from 2 to 108 days with a mean of 14.5 . CVC longevity was longer on units where certification of nurses by the PEN team was mandatory (mean 20.4 days, IR 3.5%) vs comparable units which utilized informal instruction (mean 14.4 days, IR 3.5%) . Twenty-two catheters led to patient sepsis for a rate of 3.5%, or 2.39 CVC-related infections per 1000 patient days . The preteam infection rate was 24.0%, as determined by a 6-month prospective study . Infection rates for CVCs used for TPN only and those used for parenteral nutrition (PN) plus blood products, antibiotics, and CVP measurements were identical, 3.5% . The team approach can effectively increase PN catheter longevity and reduce infection rates . Conservative cost accounting of best and worst case scenarios determined a range of $3,700 to $8,900 per episode of catheter sepsis. JPEN J Parenter Enteral Nutr, 1986 Nov-Dec, 10(6), 627 - 30 Impaired fat utilization in parenterally fed low-birth-weight infants suffering from sepsis; Park W et al.; Lipid infusion in low-birth-weight infants suffering from sepsis is still controversial . Consequently, we investigated the fat tolerance in six low-birth-weight infants with sepsis and 15 low-birth-weight infants without sepsis . For measurement of fat clearance, we assayed the serum concentrations of triglycerides enzymatically, and of the free fatty acids by colorimetric micromethod . The fatty acid oxidation was analyzed with the {13C}triolein breath test by means of ratio-mass spectrometry . The infants were maintained on continuous parenteral nutrition with various amounts of soybean oil emulsion (1 g, 2 g, and 3 g fat/kg body weight per day) . Comparing the lipid infusion of 1 and 2 g fat/kg body weight per day between the two groups, we found triglyceride and free fatty acid values in both groups to be in the normal range . At a dose of 3 g of fat/kg body weight per day, septic low-birth-weight infants showed a significantly higher concentration of triglycerides (2.02 +/- 0.46 mmol/liter) and of free fatty acids (2.06 +/- 0.45 mmol/liter) than the nonseptic low-birth-weight infants (triglycerides: 1.09 +/- 0.43 mmol/liter; free fatty acids: 1.05 +/- 0.41 mmol/liter) . The low-birth-weight infants with sepsis showed a reduced fat oxidation rate of 16.0 +/- 1.5% in contrast to that of the low-birth-weight infants without sepsis, whose rate was 38.4 +/- 1.8% . Accordingly, we apply dosages not exceeding 2 g of fat/kg body weight per day to septic low-birth-weight infants. Transfusion, 1986 Nov-Dec, 26(6), 533 - 5 Blood group incidence and Escherichia coli bacterial sepsis; Wittels EG et al.; Many strains of Escherichia coli possess an antigen that reacts with naturally occurring antibodies to human red cell B antigens . The authors tested the hypothesis that the presence of naturally occurring anti-B isoagglutinins afford protection against the development of E . coli septicemia . The blood groups found in 115 patients with E . coli septicemia were compared with those found in three "control" populations: 138 patients with septicemia due to other organisms, 23,135 hospitalized patients, and 40,038 normal blood donors . The relative incidence of B and AB blood groups (not containing anti-B antibodies) was significantly higher than A and O blood groups (containing anti-B antibodies) in the group with E . coli septicemia . This finding supports the hypothesis. Br Med J (Clin Res Ed), 1986 Oct 18, 293(6553), 983 - 8 Effects of nutrient intake, surgery, sepsis, and long term administration of steroids on muscle function; Brough W et al.; The stimulated contraction-relaxation characteristics of the adductor pollicis muscle were used to assess nutritional state in patients and healthy controls . In both groups insufficient nutrition resulted in abnormal muscle function . The ratio of force of contraction at 10 Hz to that at 20 Hz yielded the best combination of sensitivity (87%) and specificity (82%) . Sepsis resulted in abnormal muscle function, but the changes were easily distinguishable from those in subjects taking an inadequate diet . Long term administration of steroids, trauma, and surgery had no effect on muscle function . A prospective study of 11 malnourished patients with abnormal muscle function showed that all variables of muscle function returned to normal values with total parenteral nutrition . This reversal correlated significantly with the duration of parenteral nutrition and occurred before any change in anthropometric variables or plasma albumin concentration . Muscle function studies are sensitive and specific indicators of malnutrition; results depend on energy intake but are not influenced by administration of steroids, trauma, or surgery. Vestn Khir Im I I Grek, 1986 Oct, 137(10), 51 - 2 {Cardiovascular disorder syndrome in sepsis}; Pavlychev RKh et al.; The authors have observed 126 patients with sepsis and made a conclusion that all of them had cardio-vascular insufficiency . The use of hyperbaric oxygenation resulted in better activity of the cardio-vascular system. Helv Paediatr Acta, 1986 Oct, 41(4), 277 - 89 {What does neutropenia tell about the existence of sepsis in the newborn? Predictive value of clinical laboratory tests}; Kind C; A laboratory test can have one of three different functions . As a confirmatory test it can prove a diagnosis, as a screening test it can indicate the probability, that a disease in question is actually present, and as a monitoring test it can be used to guide a medical therapy . To assess the clinical value of a screening test the criteria of sensitivity, specificity and predictive value are commonly used . The meaning of these terms is explained using the example of neutropenia as a screening test for sepsis on the first day of life . For the neonates admitted during their first day of life to the neonatology units of the obstetric and paediatric departments of Zurich University a neutrophil count below 3 X 10(9)/1 as a test for sepsis has a sensitivity of 67%, a specificity of 96.7%, a predictive value of the positive test of 20%, and a predictive value of the negative test of 99.6% . The predictive value of a test is strongly dependent on the prevalence of the disease looked for in the population under study . Variation of the cut off point of a screening test results in a change of its sensitivity and predictive value of the positive test in the opposite direction. J Am Vet Med Assoc, 1986 Oct 1, 189(7), 784 - 9 Pharmacokinetic adjustment of gentamicin dosing in horses with sepsis; Sojka JE et al.; Serum gentamicin concentrations were measured and pharmacokinetic values were calculated for 12 equine patients receiving parenteral gentamicin therapy . Horses were selected for monitoring of gentamicin pharmacokinetics if they met several criteria of high risk for gentamicin-induced toxicosis . Two blood samples were obtained, one immediately before gentamicin dosing and one at 1 hour after dosing . Gentamicin serum concentrations were analyzed and dosage adjustments were made on the basis of calculated one-compartment pharmacokinetic values . Nine of the 12 horses required dosage adjustment to optimize therapeutic concentrations . Even for horses for which there was no evidence of decreased renal function, variation in the disposition of gentamicin was substantial . Because of the larger volume of distribution in foals, an initial dosage of 3 mg/kg every 12 hours was found to best approximate target concentrations . Therefore, published standard dosages were a poor means of achieving desired peak and trough concentrations in many animals . Seemingly, for optimal treatment of horses with sepsis, gentamicin dosage adjustments based on the patient's pharmacokinetic values is required. Clin Orthop, 1986 Oct, (211), 91 - 102 Clean air at operation and subsequent sepsis in the joint; Lidwell OM; When Charnley and others began to do substantial numbers of arthroplasties, they met a high incidence of subsequent failure from sepsis . There was at that time a revival of interest in the possibility that surgical sepsis originated from airborne bacteria, and engineering developments had provided the means for attaining much cleaner atmospheres . Over a period of ten years, Charnley reduced airborne contamination by more than 100-fold, and his sepsis rate fell, without using antibiotics, by tenfold . He had, however, made other procedural changes, and there were those who reported equally good results without using the ventilation and clothing systems he had devised, although usually they had given prophylactic antibiotics . The results of recent randomized studies have confirmed that considerable reduction in the sepsis rate can be obtained by operating in ultraclean air but that similarly low rates can be achieved with normal ventilation when prophylactic antibiotics are given . In addition, the two methods are effective independently, and used together sepsis rates in the joint after total arthroplasty have been reduced to a few per 1000. Arch Surg, 1986 Oct, 121(10), 1154 - 8 The effect of indomethacin on muscle and liver protein synthesis and on whole-body protein degradation during abdominal sepsis in the rat; Freund HR et al.; It has been recently suggested that increased muscle protein degradation during injury or infection is at least partially mediated by the increased production of prostaglandin E2 in muscle, and some have suggested that cyclooxygenase inhibitors might decrease protein loss in injured or septic patients . In these experiments, fractional synthesis rates of mixed muscle and liver protein and whole-body tyrosine flux were measured by constant intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with sham operations and 15 severely septic rats with or without indomethacin treatment (20 mg/kg/d) . Fractional synthesis rates in muscle and liver were decreased in late sepsis and were lowest in the septic group receiving indomethacin . Unlike the fractional synthesis rate, which was affected by indomethacin in septic rats only, tyrosine flux was significantly lower in indomethacin-treated rats with sham operations and those with sepsis . Although indomethacin reduced total-body protein breakdown during sepsis, it was also associated with lower plasma albumin levels and with decreased protein synthesis in muscle and liver at a time when the survival of the septic host may be dependent on its ability to produce new protein for a variety of vital functions . These results do not support the use of indomethacin in sepsis. Crit Care Clin, 1986 Oct, 2(4), 869 - 76 Management of sepsis following injury; Macho JR et al.; Sepsis is a significant cause of late morbidity and mortality in the severely injured patient . In addition to the risk factors of shock, multiple transfusions, and contamination, the trauma patient may have the additional factor of severe immunologic depression . The prevention of sepsis should be an early consideration . Invasive diagnostic and therapeutic maneuvers should be limited to those that are absolutely necessary, since the incidence of nosocomial infection is high . Prophylactic antibiotics should not be misused, as these may increase the risk of serious, resistant infections . Frequent examination of sputum smears may allow the early diagnosis of pneumonia . Nutritional supplementation can improve host defenses, and should be instituted early . The patient in septic shock should be resuscitated and stabilized in the intensive care unit . Monitoring should include determination of cardiac index and systemic oxygen consumption . Computed tomography has emerged as the primary modality for the diagnosis of intra-abdominal sepsis . When combined with percutaneous drainage of abscesses, it represents a rapid and safe approach to the diagnosis and treatment of the critically ill septic patient . In certain cases, such as bowel perforation or necrosis, anastomotic breakdown, or acalculous cholecystitis, laparotomy is the procedure of choice . Opportunistic infections may become significant in patients who have required a prolonged course of treatment . In the patient with multiple organ-system failure who is not responding to therapy and in whom no clear source of sepsis has been identified, exploratory laparotomy should be considered . Antibiotics should be used with caution and should not started in every patient with a fever . Their use should be directed by appropriate cultures and sensitivities.(ABSTRACT TRUNCATED AT 250 WORDS) Crit Care Clin, 1986 Oct, 2(4), 853 - 67 The cardiopulmonary effects of sepsis on the trauma patient; Demling RH; The cardiopulmonary effects of acute infection are inflammation-induced . Inflammatory mediators can both initiate and perpetuate the characteristic hyperdynamic, hypermetabolic state. Surg Gynecol Obstet, 1986 Oct, 163(4), 335 - 44 Effects of prior administration of steroids upon recovery from lethal sepsis; Hinshaw LB et al.; The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study . Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight . All dogs in group 1 (n equals six) not given steroid died within 25 hours . Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days) . All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours . Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid . Thirty-three per cent of the dogs in group 4 permanently survived . One or two daily large doses of steroid did not detrimentally affect survival of the dogs . Eight days of steroid administration suppressed endogenous cortisol production . When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited. J Foot Surg, 1986 Sep-Oct, 25(5), 351 - 6 Joint sepsis of childhood; Lawrin OR et al.; The following report dealing with joint sepsis reviews the medical and surgical techniques employed in treating a traumatically induced septic joint in a 9-year-old male . Arthrotomy of the septic joint with continuous irrigation and parenteral antibiotics proved to be more effective than closed needle aspiration or antibiotics alone. Arch Dis Child, 1986 Sep, 61(9), 903 - 5 Recurrent sepsis and gastrointestinal ulceration due to child abuse; Rubin LG et al.; An 11 year old girl developed progressive upper gastrointestinal ulceration and recurrent episodes of intravenous catheter associated polymicrobial septicaemia . Evaluation failed to establish a cause . After exclusion of the parents and careful surveillance of the patient she improved, supporting the diagnosis of suspected child abuse (a form of Meadow's syndrome). JPEN J Parenter Enteral Nutr, 1986 Sep-Oct, 10(5), 482 - 6 Utilization of Intralipid in septic rats: effects of sepsis on the clearance of exogenous fat emulsion from various organs; Chen WJ; The rats were used for the study of the effects of sepsis on the utilization of exogenous fat emulsion . The studies were carried out by measuring the rate and the pattern of clearance of intravenously-administered 14C-Intralipid from the plasma, liver, spleen, kidney, and muscle of control and septic rats . Plasma clearance of the exogenous fat measured for 14C at 30, 60, 90, 120, 360 min (n = 5) after intravenous injection revealed that the clearance was retarded by sepsis . In the liver, the initial 14C uptake was much greater in the septic rats than those in the control group (34.8 +/- 3.6% vs 14.4 +/- 1.6%, p less than 0.01) . Six hr after injection, as high as 19.6 +/- 2.4% of the injected dose was detected in the liver of the septic rats, but the control rats had only 4.4 +/- 0.8% . In spleen, kidney, and muscle, however, both the 14C uptake and the rate of its clearance were greater for the control rats than those of the septic group . The increase in the amount of liver uptake of the exogenous fat by the septic rat and the retained large amount of the fat may account for the decreased plasma clearance and the decrease in its subsequent utilization by other organs and tissues . Significant increase in liver contents of total lipid and triglyceride with a decrease in nonesterified fatty acid (NEFA) at the end of a 6-hr period in septic rats suggest that accumulation of fat in the liver may be a result of impaired triglyceride hydrolysis, possibly due to suppressed lipoprotein lipase activity. South Med J, 1986 Sep, 79(9), 1146 - 8 Nonfatal chromobacterial sepsis; Suarez AE et al.; We have described a case of multiple liver abscesses caused by Chromobacterium violaceum . This organism should be considered in any case of unexplained liver abscess occurring in the southeastern United States . Successful treatment of liver abscesses caused by this organism may be accomplished with appropriate antibiotic therapy. J Clin Gastroenterol, 1986 Aug, 8(4), 435 - 7 Wound sepsis after cholecystectomy . Influence of incidental appendectomy; O'Malley VP et al.; We undertook a prospective study of the effect of incidental appendectomy on the safety of cholecystectomy in patients under the age of 50 years . One hundred twenty patients were randomized to have either cholecystectomy alone or cholecystectomy and appendectomy . All patients received preoperative antibiotic cover . Both groups were well matched for age, sex, obesity, and length of hospital stay . Twelve patients were withdrawn from the trial . Wound infections occurred in three of the 56 patients in the cholecystectomy group (5.3%) and in two of the 52 patients in the cholecystectomy plus appendectomy group (3.8%) . Incidental appendectomy is a safe addition to elective cholecystectomy. J Trauma, 1986 Aug, 26(8), 713 - 7 Resuscitation with Fluosol-DA 20%--tolerance to sepsis; Hoyt DB et al.; Any compromise of the reticuloendothelial system (RES) or host defense in general would militate against the potential benefit of fluorocarbon emulsions as oxygen-carrying resuscitation fluids . The relationship between lethal hemorrhagic shock resuscitation with Fluosol-DA 20% and subsequent host depression was examined in a rat model . Host tolerance to a standard intra-abdominal polymicrobial septic challenge was assessed 5 days after hemorrhagic shock . Resuscitation with fluorocarbon was more effective than no resuscitation and is equal to Ringer's lactate . The addition of O2 did not enhance survival . In response to a septic challenge, survival of animals resuscitated with Ringer's lactate was similar to the control group, and fluorocarbon-treated animals had a significantly lower survival . It appears in this study that supplemental oxygen is not needed and that fluorocarbon emulsions act as a volume expander only . The enhanced mortality to a septic challenge may indicate a compromise in the host defense system induced by fluorocarbons, and clinical trials should proceed with caution accordingly. Arch Surg, 1986 Aug, 121(8), 918 - 23 Protein metabolism in different types of skeletal muscle during early and late sepsis in rats; Hasselgren PO et al.; Protein synthesis and degradation rates were measured in incubated soleus (SOL) and extensor digitorum longus (EDL) muscles 4, 8, and 16 hours following cecal ligation and puncture (CLP) in rats . No significant differences in protein synthesis between septic and control rats were found . The proteolytic rate in SOL muscle was increased by 36% eight hours after CLP and by 42% 16 hours after CLP . In EDL muscle, protein breakdown was not significantly increased until 16 hours after CLP, at which time it was 53% above the control value . The plasma amino acid pattern became increasingly deranged during the course of the study, and at 16 hours almost all individual amino acid levels were significantly different in septic rats compared with control rats . There was a significant positive correlation between plasma concentrations of phenylalanine, histidine, and ornithine and the proteolytic rate in EDL and SOL muscles, with the best correlation being found between phenylalanine concentration and proteolytic rate in SOL muscle . These results suggest that muscle wasting during sepsis is caused by increased protein breakdown, not by decreased protein synthesis, and that accelerated muscle proteolysis is an early phenomenon in sepsis. Arch Surg, 1986 Aug, 121(8), 897 - 901 Multiple-organ failure and sepsis without bacteria . An experimental model; Goris RJ et al.; Multiple-organ failure is generally attributed to bacterial infection, although a correlation with positive blood cultures is not consistently found . Consequently, we studied the effects of a local nonbacterial inflammatory stimulus on distant organ functions and metabolism . Wistar rats were inoculated intraperitoneally with zymosan . Heart and ventilatory rates, oxygen consumption, and body temperature were measured . Survivors were killed at day 12 for blood analysis, weighing of organs, and microscopy . Intraperitoneal zymosan resulted in an early hyperdynamic "septic" response with a 35% mortality . After a few days, oxygen consumption decreased, serum lactate levels increased, and the function of multiple organs deteriorated, while blood cultures remained sterile . The experiment was repeated in germ-free rats with similar results but a lower mortality . We concluded that a severe inflammatory response in itself is capable of inducing multiple-organ failure with "sepsis." Surgery, 1986 Aug, 100(2), 222 - 8 Reduced muscle amino acid uptake in sepsis and the effects in vitro of septic plasma and interleukin-1; Hasselgren PO et al.; Inhibited amino acid transport in skeletal muscle during sepsis has been demonstrated previously . In the present study we investigated the effects in vitro of plasma from septic animals or fractions of septic plasma that contain solutes with a molecular weight less than 30,000 daltons or less than 2000 to 3000 daltons on amino acid transport in incubated rat soleus (SOL) muscles . The influence of interleukin-1 (IL-1), prostaglandin E2 (PEG2), and the "catabolic" hormones corticosterone, glucagon, and epinephrine on muscle amino acid uptake was also investigated . Amino acid transport was studied with 3H-alpha-aminoisobutyric acid (AIB) . Whole-septic plasma and the two low molecular-weight fractions of the septic plasma reduced muscle amino acid uptake by about 20% . IL-1 or PGE2 did not affect amino acid transport . When the catabolic hormones were added individually to incubated SOL muscles, no changes in AIB uptake were noticed . When glucagon or epinephrine was added in combination with corticosterone or when all three hormones were added together, amino acid transport was reduced by 10% to 15% . The results suggest that inhibited muscle amino acid uptake in sepsis is caused by a circulating factor(s) with a molecular weight less than 2000 to 3000 daltons . A synergistic action among the catabolic hormones may be one important factor for reduced muscle amino acid transport in sepsis. Akush Ginekol (Mosk), 1986 Aug, (8), 21 - 3 {Current treatment of postabortion sepsis}; Grishchenko VI et al.; PIP: The results of combined treatment of 83 women (17-43 years old) with septic complications following abortion in a nonhospital setting are reviewed . The group included 9 primigravida and 74 secundigravida . Almost all women had a history of extragenital diseases and 52 had a history of genital tract inflammations . Pregnancy was terminated in the first trimester in 56 and in second trimester in 27 . Septic complications (endometritis and adnexitis) developed on day 2-20 after abortion . Of 83 patients, 10 (12%) died in spite of prolonged and unsuccessful treatment . 22 women with diffuse peritonitis and peritoneal abscess underwent surgery (extirpation of the uterus and tubes in 17, supravaginal amputation of the uterus in 1, and opening of the abscess in 4) and 51 underwent curettage of the uterine cavity . Postoperative treatment included antibiotics, administration of plasma substitutes, heparin, correction of electrolyte imbalance, administration of immunostimulants, and transfusion of the autologous blood irradiated with ultraviolet rays . Antibiotic therapy usually consisted of at least 2 drugs in maximum doses (1 antibiotic was given iv) . The most frequent combination was penicillin (6-8 g/day) together with aminoglycosides or cephalosporins . Antibiotics were given for 7-10 days . Indications for extirpation of the uterus and tubes included anaerobic septic process in the uterus, dissemination of the infection outside the uterus, renal-hepatic failure, perforation or necrosis of the uterine wall . Instead of peritoneal dialysis, the patients received irrigation of the peritoneal cavity with a mixture of kanamycin, furagin and novocain . All 72 patients survived surgery or curettage and were cured . JPEN J Parenter Enteral Nutr, 1986 Jul-Aug, 10(4), 351 - 5 Regulation of glucose metabolism by altered pyruvate dehydrogenase activity . I . Potential site of insulin resistance in sepsis; Vary TC et al.; Regulation of the pyruvate dehydrogenase (PDH) complex has been demonstrated to be a key mechanism in the control of carbohydrate oxidation and conservation of glucose carbon . The effect of sterile inflammation and chronic sepsis (small and large abscess) on the activity of the PDH complex was examined in liver and skeletal muscle . Sepsis altered the proportion of PDH in the active, dephosphorylated form . In hepatic tissue, sterile inflammation leads to a 2.5-fold increase in the proportion of active PDH complex compared to fed control . The same increase in the proportion of active PDH complex was observed in rats with a small septic abscess . However, when the severity of septic episode was increased, the proportion of active PDH complex decreased relative to sterile inflammation or small septic abscess animals . A different pattern in the response to sterile inflammation and sepsis on the proportion of active PDH complex was observed in skeletal muscle compared to liver . In contrast to liver, sterile inflammation did not alter the proportion of active PDH in skeletal muscle . In addition, sepsis (either small or large septic abscess) resulted in a 3-fold decrease in the proportion of active PDH relative to fed control or sterile inflammatory animals . The decrease in the proportion of active PDH complex in sepsis was associated with a corresponding increase in the skeletal muscle acetyl-CoA/CoA ratio . The mechanism responsible for lowered PDH complex activity may have been due to increased PDH kinase activity, secondary to increased skeletal muscle acetyl-CoA/CoA ratios. Med Clin North Am, 1986 Jul, 70(4), 921 - 32 Clinical indicators in sepsis and septic adult respiratory distress syndrome; Jacobs ER et al.; Sepsis and septic ARDS remain clinical problems of great significance because of the numbers of patients affected each year and the high mortality associated with development of the syndrome . The standard therapies for these conditions, judicious antibiotic administration and supportive care, continue to be the mainstays of treatment for these patients, but mortality even with optimal conventional therapy is between 50% and 90% for septic ARDS . The mortality for an individual patient may be anticipated to be substantially higher or lower than these average reported values, based on the presence or absence of several clearly identified risk factors, such as advanced age, shock, evidence of multiorgan system failure, and others discussed above . Similarly, the likelihood that the septic patient will develop ARDS is increased by the appearance of shock and thrombocytopenia . Two therapies that are used extensively in the intensive care unit today--corticosteroid administration and PEEP--have not been shown to reduce the overall mortality of sepsis or septic ARDS . Newer therapeutic modalities, designed to protect against or reverse cardiovascular consequences of sepsis, reduce the incidence of multiorgan system failure, and diminish the high incidence of uncontrolled infections in these patients, are needed; investigations of these interventions are in progress. J Trauma, 1986 Jul, 26(7), 625 - 30 Immunomodulating drugs increase resistance against sepsis in traumatized mice; Hansbrough JF et al.; Immune suppression occurs frequently after major injury and undoubtedly contributes to infection and mortality in trauma patients . Prevention of such suppression may lead to decreased infection and improved survival in trauma patients surviving the immediate insult of injury . Suppressor-cell activation appears to play a key role in immune suppression after major injury . For several years we have studied the effects on immune functions after injury of various drugs which have been shown in the immunologic literature to have inhibitory effects on suppressor cell populations . H2-antagonists may inhibit suppressor cell activation by blocking surface H2-receptors, which are present in higher numbers on suppressor cells than on helper cells . Prostaglandin inhibitors may block the multiple immune suppressive effects of prostaglandins, particularly PGE2 . Immunological studies suggest that low-dose cyclophosphamide selectively inhibits the proliferation of suppressor T cells . Our previous work suggested that such drugs preserve cell-mediated immune functions after injury . In experiments reported here, we utilized a standard hindlimb crush injury and amputation in mice, followed in 24 hrs by polymicrobial septic challenge using cecal ligation and 23-gauge needle puncture (CLP) . Nontraumatized (control) mice had a 36.2% mortality after CLP; when crush injury/amputation was followed by CLP in 24 hrs the mortality rose to 63.8% (p less than 0.0035) . When mice were given 24 hrs before crush/amputation: cimetidine, an H2-antagonist (10 mg/kg/day); ibuprofen, a prostaglandin blocker (5 mg/kg/day); or cyclophosphamide (2.5 mg/kg/day), and a second dose on the day of trauma, with CLP 24 hrs later, subsequent mortality was not different from the mortality in nontraumatized, control mice (p less than 0.0035).(ABSTRACT TRUNCATED AT 250 WORDS) J Rheumatol, 1986 Jun, 13(3), 647 - 8 The seal finger: an unusual case of monoarticular sepsis; Bykerk VP et al.; We describe a case of monoarthritis in an Inuit seal hunter which progressed to joint destruction of the distal interphalangeal joint despite early and aggressive sequential antibiotic therapy with ampicillin, cloxacillin and penicillin G . In retrospect, had the entity of seal finger been diagnosed at the onset, appropriate antibiotic therapy with tetracycline may have prevented permanent joint damage. Am Surg, 1986 Jun, 52(6), 294 - 8 Non-directed relaparotomy for intra-abdominal sepsis . A futile procedure; Bunt TJ; Over a 50-month period, 2,657 primary laparotomies were performed; 192 patients underwent urgent relaparotomy for complications of primary laparotomy . Forty-seven relaparotomies were performed for Type I intra-abdominal sepsis (IAS-1) with a 12.8 per cent mortality, and 46 for Type 2 IAS with a 82.6 per cent mortality (P less than 0.001) . Of the 46 IAS-2 patients, 31 relaparotomies were "directed" by positive peritoneal signs (CAT/ultrasound/PIPIDA examinations) with 94 per cent (29/31) yielding positive findings . Fifteen were "non-directed" in an effort to uncover an occult source of continuing sepsis of MOSF and yielded a 13 per cent (2/15) positive rate (P less than 0.001), and a 93 per cent (14/15) mortality . Relaparotomy for sepsis directed by positive radiologic or clinical findings can be reliably expected to demonstrate a surgical focus whose correction may yield patient survival; non-directed relaparotomy, however, seldom demonstrates a focus and does not contribute to survival. Surgery, 1986 Jun, 99(6), 744 - 51 Interaction of prostaglandins, activated complement, and granulocytes in clinical sepsis and hypotension; Slotman GJ et al.; Activated complement, thromboxane A2, prostacyclin, and activated granulocytes have been implicated in hemodynamic dysfunction after trauma, in sepsis, and in hypovolemic and septic shock . This study evaluated the interaction of plasma concentrations of complement components C3a and C5a, thromboxane B2 (TxB), prostaglandin 6-keto-F1 alpha (PGI), and granulocyte aggregation in clinical sepsis and hypotension . Forty-eight critically ill patients were followed clinically for as long as 10 days . Plasma C3a, C5a, TxB, and PGI were measured daily by the radioimmunoassay method . Granulocyte aggregation, the percentage of maximum aggregation of zymosan-activated plasma standard curves, was performed with patient plasma and normal human leukocytes . Patients were studied in four groups: group I, nonseptic, normotensive; group II, hypovolemic shock, group III, normotensive severe sepsis; and group IV, septic shock . Plasma from 12 normal adults was the control value . PGI, TxB, C3a, C5a, and granulocyte aggregation in patients were greater than that in the control subjects . Granulocyte aggregation was increased in groups III and IV versus groups I and II . C3a was increased in group IV versus groups II and III . C5a and TxB did not vary between groups . PGI was greatly increased in group IV compared with groups I through III . C3a and C5a decreased in nonsurvivors . PaO2/FiO2 ratios correlated directly with PGI and inversely with C3a and TxB/PGI . Plasma PGI and C3a are increased in septic shock . C3a and TxB/PGI imbalances are involved in hypovolemic and septic shock. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1986 May, 19(2), 104 - 11 Effects of exogenous fat emulsion (Intralipid) on chemotactic function of monocytes and polymorphonuclear cells in sepsis; Chen WJ et al.; Effects of exogenous fat emulsion (Intralipid) on the chemotactic function of monocytes and polymorphonuclear (PMN) cells were studied in vivo with rats . Abdominal sepsis was induced in Sprague Dawley rats by cecal ligation and puncture . Following a bolus infusion of the fat emulsion or saline, chemotactic function of monocytes and PMN cells was evaluated in animals divided into the following four groups: Group I, non-septic rats receiving saline infusion (NS-S); Group II, non-septic rats receiving the fat emulsion (NS-F); Group III, septic rats receiving saline (S-S); Group IV, septic rats receiving the fat emulsion (S-F) . Results of the study revealed that monocyte function was suppressed by the sepsis, whether saline or the fat emulsion was infused, and administration of the fat emulsion resulted in suppression of monocyte chemotaxis both in the non-septic and the septic rats . Although in this study chemotactic function of PMN cells was not significantly suppressed by the sepsis, administration of the fat emulsion again led to a suppression of PMN cell function, in both the non-septic and the septic rats . Results of the study confirmed that administration of an exogenous fat emulsion may suppress the chemotactic function of the monocytes and PMN cells and, in the presence of severe sepsis, infusion of the fat emulsion may lead to a further deterioration of immunologic function of the host . Special care, therefore, should be taken against the use of exogenous fat emulsion in septic individuals or in those at risk of infection. JPEN J Parenter Enteral Nutr, 1986 May-Jun, 10(3), 253 - 7 Endocrine mediators of metabolism associated with injury and sepsis; Dahn MS et al.; We have studied the endocrine characteristics of 13 seriously ill patients with the use of a provocative intravenous glucose bolus . Notable in this stressed patient population was that no major interpatient differences in response to glucose were found for insulin, glucagon, cortisol, or epinephrine . However, following glucose challenge half of this group (7/13) exhibited a prominent "paradoxical" mean human growth hormone (hGH) elevation (26.4 +/- 9.3 microU/ml) whereas the others (6/13) exhibited only a minor increase (7.8 +/- 2.9 microU/ml) . In addition, norepinephrine levels were significantly higher in the latter group suggesting that the adrenergic nervous system plays a major role in regulating hGH in stress. Can J Surg, 1986 May, 29(3), 194 - 7 Host-defence mechanisms in surgical patients: case report of reduced polymorphonuclear neutrophil and antibody functions associated with surgical sepsis; Nohr CW et al.; The authors evaluated the host-defence capability of a 33-year-old woman with a history of poor wound healing, gastrointestinal fistulas and bacterial and fungal sepsis after abdominal operations . The following tests gave normal results: hemoglobin, blood neutrophil and monocyte counts, delayed hypersensitivity skin test, serum albumin, immunoglobulin and complement levels, blood T- and B-cell percentages, in-vitro immunoglobulin synthesis and body cell mass . The following tests gave abnormal results: lymphocyte count, leukocyte adherence, in-vivo and in-vitro polymorphonuclear neutrophil chemotaxis, neutrophil bacterial killing and antibody response to tetanus toxoid . Decreased polymorphonuclear neutrophil and humoral immune functions could account for the woman's history of repeated surgical sepsis . Evaluation of host-defence mechanisms can illuminate the cause of repeated episodes of sepsis. Br J Surg, 1986 May, 73(5), 371 - 2 Inci