Q J Med, 1989 Nov, 73(271), 1037 - 43 Primary sepsis presenting as fulminant hepatic failure; Dirix LY et al.; Four patients who were referred to the Liver Failure Unit with an initial diagnosis of fulminant hepatic failure were found to have severe bacterial infection from a primary septic focus as the cause of their illness . Clinical and biochemical characteristics were not helpful in differentiating these patients from those with hepatic failure from other causes, and only a high degree of suspicion will prevent delay in the diagnosis of underlying sepsis and initiation of appropriate treatment . The possible mechanisms responsible for this uncommon association are discussed. J Hepatol, 1989 Nov, 9(3), 287 - 94 Reticuloendothelial function and plasma fibronectin in a murine model of intra-abdominal sepsis; Jones GE et al.; The lung is the target organ most frequently involved in the early phase of multiple organ failure . Microembolisation of the pulmonary vasculature by bacterial and non-bacterial particles and debris with failure of the clearance mechanism of the reticuloendothelial system (RES) and depletion of plasma fibronectin have been implicated in the pathogenesis . The present study examined the concurrent changes in plasma fibronectin, RES phagocytic function, organ localisation of bacterial and non-bacterial particles and the levels of circulating endotoxin and fibrin degradation products in a clinically relevant murine model of severe intra-abdominal infection . Progressive sepsis was associated with deteriorating RES phagocytic function to 45% of control values within 48 h of sepsis induction . There was decreased hepatosplenic uptake and increased pulmonary localisation of bacterial and lipid emulsion particles . Plasma fibronectin increased in septic animals within 48 h suggesting increased fibronectin production . These changes would support the hypothesis that altered RES function may facilitate pulmonary microembolisation in the pathogenesis of septic multiple organ failure. Circ Shock, 1989 Nov, 29(3), 229 - 44 Eicosanoids and the hemodynamic course of live Escherichia coli-induced sepsis in baboons; Camporesi EM et al.; Time-related changes in eicosanoid release and hemodynamic parameters were characterized in baboons during the early development of sepsis induced by intravenous (i.v.) infusion of live Escherichia coli (4 x 10(10) organisms/kg) in baboons . Plasma levels of thromboxane B2 (TxB2), a stable metabolite of thromboxane A2 (TxA2), rose rapidly in arterial, venous, and pulmonary arterial blood after infusion of live E . coli, attaining maximal increases at 30 min and returning to control values by 60 min . In contrast, plasma concentrations of 6-keto-PGF1 alpha rose slowly after infusion, reaching peak concentrations at 120 min, then slowly returned to control values between 4 and 5 hr after infusion of live E . coli . Hemodynamic values remained stable during the first 2 hr after infusion, although early changes in cellular energy metabolism and incipient hemodynamic failure were inferred from pyrexia, tachycardia, and metabolic acidosis . At 3 hr, signs of further hemodynamic compromise developed, including increased venous PCO2, reduced pulmonary capillary wedge pressure, and reduced stroke volume, followed by gradual increases in systemic and pulmonary vascular resistance . These factors coincided with progressive reductions in cardiac output and deteriorating circulatory efficiency . The time course of events following infusion of live E . coli indicates that alterations in cellular energy provision occurred early (within 1 hr), whereas central hemodynamic parameters decayed much more slowly . Additionally, TxA2 and PGI2 appear related to the early events in the development of sepsis as their release preceded cardiocirculatory failure. Metabolism, 1989 Nov, 38(11), 1070 - 6 Epinephrine-induced increase in glucose turnover is diminished during sepsis; Hargrove DM et al.; The responsiveness of septic rats to epinephrine-induced alterations in carbohydrate metabolism was studied . Nonlethal sepsis was produced by subcutaneous injections of live Escherichia coli over 18 hours in conscious catheterized rats . Glucose kinetics were assessed by IV infusion of {6-3H}-glucose . After two hours of tracer infusion, blood samples were taken for basal values . Thereafter, epinephrine was infused at 0, 0.05, 0.2, or 1.0 microgram/min/kg for an additional four hours . Compared with nonseptic rats, septic animals had increased basal values for glucose rate of appearance (Ra, 63%), glucose clearance (86%), and plasma lactate concentration (133%) . Infusion of epinephrine resulted in dose-dependent increases in glucose Ra, as well as plasma glucose and lactate concentrations, and decreases in glucose clearance and muscle glycogen content . At each dose of epinephrine, the increases in response from basal of plasma glucose and glucose Ra in septic rats were 50% or less of that observed in nonseptic animals . There were no differences between septic and nonseptic rats in plasma lactate and glucose clearance responses from basal or in circulating levels of catecholamines achieved during the epinephrine infusion . The present results indicate that septic rats are less responsive than control animals to epinephrine-induced increases in glucose turnover. J Lab Clin Med, 1989 Nov, 114(5), 579 - 86 Metabolic control of hepatic gluconeogenesis in response to sepsis; Ardawi MS et al.; The regulation of hepatic gluconeogenesis was studied in rats made septic by cecal-ligation and puncture technique . Blood glucose was not significantly different in septic rats, but lactate, pyruvate, and alanine were markedly increased . Conversely, blood ketone body concentrations were markedly decreased in septic rats . Both plasma insulin and glucagon were markedly elevated in septic rats . The maximal activities of glucose 6-phosphatase, fructose 1,6-biphosphatase, pyruvate carboxylase, and phosphenolpyruvate carboxykinase were decreased in livers obtained from septic rats suggesting a diminished hepatic gluconeogenesis . Hepatic concentrations of lactate, pyruvate, and other gluconeogenic intermediates were markedly increased in septic rats, whereas those of fructose 2,6-bisphosphate and acetyl-CoA were decreased . The rate of gluconeogenesis from added lactate, pyruvate, alanine, and glutamine was decreased in isolated incubated hepatocytes from septic rats . It is concluded that the diminished capacity of hepatic gluconeogenesis of septic rats could be the result of changes in the maximal activities or regulation of key nonequilibrium gluconeogenic enzymes or both but do not exclude other factors (e.g., toxins). Circ Shock, 1989 Nov, 29(3), 219 - 27 Changes in hemorheology in patients with sepsis or septic shock; Voerman HJ et al.; We studied hemorheological variables in ten consecutive patients with sepsis or septic shock . One patient with sepsis, eight with septic shock, and one with the toxic shock syndrome were included . The patients were studied during the first 3 days and the eighth day of their illness . All patients except one survived 1 week . Final outcome showed a 50% mortality . A decrease in low shear blood viscosity of red blood cells (RBC) suspended in plasma was observed . This indicates a decrease in RBC aggregation . These changes persisted during the first week . The decrease in RBC aggregation occurred despite a normal plasma viscosity . No correlations were found between the reduction in RBC aggregation and changes in blood chemistry, amounts of dopamine or plasma administered, or with the APACHE II score . A decrease in RBC deformability was observed, due to changes in the RBC membrane . After 1 week, these changes had disappeared . The change in RBC deformability during the study period was significantly related to changes in the amount of dopamine administered. Circ Shock, 1989 Nov, 29(3), 181 - 91 Importance of hyperglucagonemia in eliciting the sepsis-induced increase in glucose production; Lang CH et al.; The plasma concentration of various catabolic hormones, including glucagon and catecholamines, is elevated in sepsis . Furthermore, the infusion of these hormones into control animals increases the rate of glucose production . Previous studies by our laboratory have demonstrated that adrenergic blockade alone is not able to reverse or prevent the sepsis-induced increase in glucose metabolism . Therefore, the purpose of the present study was to determine whether the sepsis-induced hyperglucagonemia was important to maintain the elevation in glucose metabolism . Hypermetabolic sepsis was produced in chronically catheterized conscious rats by repeated subcutaneous injections of Escherichia coli . Glucose kinetics, assessed by the constant i.v . infusion of {6-3H}- and {U-14C}-glucose, were determined in septic and nonseptic rats prior to and for 3-4 hr after the infusion of somatostatin with or without insulin replacement . Sepsis increased the rate of glucose appearance (80%), recycling (276%), and metabolic clearance (88%), as well as the plasma lactate concentration (140%), compared to nonseptic rats . Lowering both the insulin and glucagon concentration with somatostatin did not attenuate the sepsis-induced increases in glucose metabolism . However, when the hyperglucagonemia was selectively reduced by replacing insulin, and euglycemia was maintained by a glucose infusion, the elevated rate of endogenous glucose production returned to levels not different from nonseptic animals . In contrast, the sepsis-induced elevation of glucose clearance was unaltered under these conditions . These results indicate that during hypermetabolic sepsis the elevated glucagon level is an important mediator of the enhanced rate of gluconeogenesis. Br J Surg, 1989 Nov, 76(11), 1144 - 6 Wound sepsis following Ramstedt pyloromyotomy; Rao N et al.; Wound sepsis is common following pyloromyotomy in children and in a retrospective study of 178 cases the incidence of wound infection was 21 (11.8 per cent) . On preliminary analysis, three variables were associated with wound sepsis: age, duration of projectile vomiting and surgical technique . Only surgical technique was found to be statistically significant on sequential multivariate analysis . Mass closure with polydioxanone was associated with a 1 per cent (one of 70) wound sepsis rate . Wound sepsis after pyloromyotomy is dependent on technique, and mass closure with polydioxanone is recommended . The routine use of tension sutures should be abandoned. J Trauma, 1989 Oct, 29(10), 1362 - 6 The declining incidence of fatal sepsis following thermal injury; Merrell SW et al.; Successful management of burned patients requires effective prevention and management of infectious complications . This study reviews the incidence of fatal sepsis in our burn center and attempts to analyze factors which may predict septic mortality . From January 1, 1978, through May 31, 1988, 1,913 patients were admitted, with a mean age of 24.8 +/- 0.5 years, a mean burn size of 17.7 +/- 0.4% total body surface area (%TBSA), and a mean 10.1 +/- 0.5% TBSA full-thickness injury . Nine per cent of patients sustained concurrent inhalation injuries . Overall mortality was 7.4%, and 1.6% of patients died from sepsis . Regression analysis showed that overall burn size, presence of inhalation injury, and the extent of full-thickness burn injury were significant independent predictors of death from sepsis, in decreasing order of relative importance . During the period 1983-1988, the incidence of septic mortality was 0.7%, which was significantly lower than the earlier half (1978-1982) of the study period (p less than 0.01) . These data indicate that fatal infections are becoming increasingly uncommon after thermal injury . The reasons for this decline are probably multiple, and they include the widespread practice of early excision, and improvements in fluid resuscitation and the general medical care of burned patients. Surgery, 1989 Oct, 106(4), 718 - 22; discussion 722-4 In vitro polymorphonuclear neutrophil function in surgical patients does not correlate with anergy but with "activating" processes such as sepsis or trauma; Christou NV et al.; We studied 199 preoperative patients admitted for esophagogastric, gastric, colonic, or rectal resections, 132 patients with severe blunt trauma, 180 surgical intensive care unit patients with major sepsis, and 95 laboratory controls in order to clarify the role of polymorphonuclear neutrophil (PMN) adherence and chemotaxis to outcome . Patients were also stratified by the delayed-type hypersensitivity response to five ubiquitous antigens . PMN adherence and PMN chemotaxis were not different in preoperative reactive or anergic patients and were equal to the control values, whereas both reactive patients and anergic patients showed altered PMN function after trauma or sepsis . There was no difference in PMN adherence or chemotaxis between patients who died and those who lived . Multiple logistic regression analysis showed that patient age, delayed-type hypersensitivity, and admission serum albumin level, not PMN adherence or chemotaxis, were significantly related to septic mortality . We concluded that altered circulating PMN adherence and chemotaxis is seen in all patients after an "activation" event such as trauma or sepsis . This is a nonspecific immune alteration not related to specific immune events such as delayed-type hypersensitivity; it does not correlate with patient outcome and should not be used as a predictive variable. Orthop Clin North Am, 1989 Oct, 20(4), 709 - 21 Ankle arthrodesis in the presence of ongoing sepsis . Indications, methods, and results; Cierny G 3rd et al.; The prognosis for ankle arthrodeses performed in the presence of chronic joint sepsis is addressed . The described methods afford reliable and highly successful results, even in cases with massive hard- and soft-tissue deficits . An ankle fusion can be reliably accomplished in the presence of wound contamination, inadequate bone stock, and an ischemic soft-tissue envelope . The methods used must be tailored to the anatomic extent of disease, the physiologic condition of the host, and institutional resources. Crit Care Med, 1989 Oct, 17(10), 975 - 8 Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans; Damas P et al.; In a study of serum levels of tumor necrosis factor (TNF alpha) and interleukin-1 beta (IL-1 beta) in patients developing sepsis in the ICU, high TNF alpha levels were found in patients with septic shock . Normal values are 75 +/- 15 pg/ml; in these patients, TNF alpha serum level ranged from 100 to 5000 pg/ml with a mean of 701 +/- 339 pg/ml and a median of 250 pg/ml . There was a correlation between TNF alpha level and sepsis severity score as well as with mortality . In contrast, IL-1 beta serum levels were only slightly increased and were not correlated with severity or mortality. Blood, 1989 Oct, 74(5), 1704 - 10 Increased plasma levels of interleukin-6 in sepsis; Hack CE et al.; Interleukin-6 (IL-6) is likely to be an important mediator of the inflammatory response . We measured levels of this cytokine in plasma samples from 37 patients with sepsis or septic shock obtained at the time of admission to the intensive care unit and related these levels to hemodynamic and biochemical parameters as well as to clinical outcome . In 32 of the 37 patients, increased levels of IL-6 were found, occasionally up to 7,500 times the normal level . The highest IL-6 levels were encountered in patients who suffered from septic shock (P value of the difference between patients with and without shock less than .0001) . In addition, IL-6 significantly correlated with plasma lactate (P less than .0001), heart rate (P = .05) and, inversely, with mean arterial pressure (P = .01) and platelet counts (P = .0002) . Significant correlations of IL-6 with the anaphylatoxins C3a (P = .0001) and C4a (P = .0002) and with the main inhibitor of the classical pathway of complement, C1-inhibitor (inverse correlation, P = .05), were also observed . IL-6 on admission appeared to be of prognostic significance: levels were higher in septic patients who subsequently died than in those who survived (P = .0003), in particular when only patients with septic shock were considered (P less than .0001) . All nine septic patients with levels of less than 40 U/mL on admission survived, whereas 89% of the nine patients with levels exceeding 7,500 U/mL died . These data provide evidence for a role of IL-6 in the pathophysiology of septic shock . Further studies are needed to reveal whether IL-6 in sepsis is directly involved in mediating lethal complications or whether it is to be considered as an "alarm hormone" that reflects endothelial cell injury probably mediated by the anaphylatoxines. Crit Care Clin, 1989 Oct, 5(4), 785 - 92 CNS effects of sepsis; Bowton DL; Multiple systems organ failure in association with sepsis has a distressingly high mortality rate . The spectrum of neurologic deficits and their incidence in septic patients remains poorly characterized . However, sepsis-associated CNS dysfunction appears to be as important a harbinger of excess mortality as renal or pulmonary dysfunction in septic patients . Brain microabscesses, disordered amino acid metabolism, alterations in brain neurotransmitters, and reduced cerebral blood flow and oxygen utilization have all been proposed as potential etiologies of septic encephalopathy . Unfortunately, much remains to be elucidated regarding the presentation and pathophysiology of septic encephalopathy before consideration of what constitutes appropriate therapy is likely to be fruitful . The dietary manipulation of plasma and brain amino acid profiles and refinement of therapeutic objectives of cardiovascular support to improve regional organ blood flow are but two promising areas of current investigation . At the present time, however, meticulous supportive therapy, appropriate antibiotics, and surgical drainage of a septic focus, when possible, represent optimal therapy. Am Rev Respir Dis, 1989 Oct, 140(4), 974 - 80 The effects of aminophylline and pentoxifylline on multiple organ damage after Escherichia coli sepsis; Harada H et al.; We studied the effects of the methylxanthines, aminophylline (AMPH) and pentoxifylline (PTXF), on multiple organ damage following Escherichia coli sepsis in guinea pigs . To assess multiple organ damage, 125I-labeled albumin accumulation was measured in bronchoalveolar lavage (BAL) fluid, lung, kidneys, liver, heart, adrenal glands, and spleen and expressed as a ratio of BAL fluid or tissue to 125I-labeled albumin plasma (albumin index: Al) . Wet-to-dry lung weight (W/D) ratios were also measured . The methylxanthines were administered by a bolus injection followed by a continuous infusion . The seven experimental groups included: saline-control, AMPH-control, PTXF-control, E . coli septic-control, E . coli septic-AMPH high dose, E coli septic-AMPH low dose, and E . coli septic-PTXF . The AI of the BAL fluid and all examined organs significantly increased in the septic-control group compared to those in the saline-, AMPH-, and PTXF-control groups, In all septic-methylxanthine groups, the AI of the BAL fluid and all organs, except for the spleen, were significantly lower than those of the septic-control group . Compared to the saline-, AMPH-, and PTXF-control groups, the septic-control group revealed a significant increase in lung W/D ratios, whereas the septic-AMPH high and low dose groups and the septic-PTXF group did not . Of importance, the septic-PTXF group did not cause a significant decrease in mean arterial pressure (MAP) as compared to the control groups, whereas the septic-AMPH groups did cause a significant decrease in MAP compared to the septic-control group . Therefore, the data from this experiment demonstrate that both AMPH and PTXF attenuate the multiple organ albumin leak seen in septic guinea pigs . However, PTXF exerted this protective effect with no discernible effect on the MAP whereas the MAP of AMPH-treated guinea pigs was significantly decreased. Crit Care Med, 1989 Sep, 17(9), 886 - 8 Sinusitis: hidden source of sepsis in postoperative pediatric intensive care patients; Bos AP et al.; Paranasal sinusitis is reported as a complication of prolonged nasal intubation and the source of sepsis in adult intensive care patients . In surgical neonates with congenital malformations, prolonged intubation with a nasotracheal (NT) or NG tube is often necessary, but sinusitis with complicating sepsis is seldom reported . Sinus x-rays may confirm the diagnosis; in infancy, prolonged nasal intubation delays the pneumatization of the sinuses and the mastoids, resulting in additional diagnostic problems . In a 1-yr period, we saw three patients with multiple septic episodes in which the source of sepsis was undetectable . Despite the absence of clinical symptoms and radiologic evidence of sinusitis or mastoiditis, surgical drainage revealed pus and led to the disappearance of septic episodes and ear, nose, and throat problems . There is an association between prolonged NT and NG intubation, and sinusitis or mastoiditis as an unrecognized source of sepsis in young infants . Absence of radiologic evidence of sinusitis or mastoiditis causes pitfalls in diagnosis and is related to delayed pneumatization of the sinuses and the mastoid in prolonged nasal intubation in young infants. Clin Pediatr (Phila), 1989 Sep, 28(9), 423 - 5 Fusiform bacterial sepsis . Metastases with osteomyelitis and hepatic abscess occurring in a chaotic family; Van Dyke DC et al.; Cases of fusiform bacteria sepsis have been reported infrequently in the pediatric literature . This case demonstrates the severe metastatic complications of fusiform bacterial sepsis including osteomyelitis, with multiple pathological fractures, sepsis, and abscesses of the liver . In the diagnostic evaluation of the etiology for this uncommon infection, child abuse was discovered in all children of this family . In children with uncommon infections and no underlying etiology, child abuse should be considered. Acta Chir Scand, 1989 Sep, 155(9), 445 - 9 Ranitidine for improvement of delayed hypersensitivity response in patients with sepsis; Nielsen HJ et al.; Twenty-five patients admitted to intensive or high-dependency surgical care units were randomized to receive ranitidine intravenously 50 mg every 6 hours for 8 days or no ranitidine . All had septicemia or intra-abdominal sepsis, with body temperature greater than or equal to 38.5 degrees C for more than 48 hours despite comprehensive medical and/or surgical treatment . Cell-mediated immunity was assessed by skin testing with seven common delayed type hypersensitivity antigens applied on days 1, 4 and 7 and all tests were read at 48 hours, i.e . on days 3, 6 and 9 . The ranitidine/non-ranitidine regimen was initiated on day 1 and continued until day 9 . Severity of illness was evaluated before and 3, 6 and 8 days after initiating the study, using the APACHE II scoring system . The scores before and during the study were similar in the ranitidine and non-ranitidine groups . Delayed type hypersensitivity improved in patients treated with ranitidine (p less than 0.001), but was unchanged in the untreated group (p greater than 0.7) . These observations may suggest potential beneficial effects of ranitidine therapy in patients with trauma-induced immunosuppression. Am J Physiol, 1989 Sep, 257(3 Pt 1), E323 - 31 Role of insulin and glucose oxidation in mediating the protein catabolism of burns and sepsis; Jahoor F et al.; We have investigated the responsiveness of protein kinetics to insulin and the role of glucose oxidation rate as a mediator of the protein catabolic response to burn injury and sepsis by assessing the response of leucine and urea kinetics to a 5-h hyperinsulinemic euglycemic clamp with and without the simultaneous administration of dichloroacetate (DCA) (to further increase glucose oxidation via stimulation of pyruvate dehydrogenase activity) in eight severely burned and eight septic patients . Leucine and urea kinetics were measured by the primed-constant infusions of {1(-13)C}leucine and {15N2}urea . Compared with controls, basal leucine kinetics (flux and oxidation) were significantly elevated (P less than 0.01) in both groups of patients . Hyperinsulinemia elicited significant (P less than 0.05) decreases in leucine kinetics in both groups of patients . Consistent with this observation, hyperinsulinemia caused urea production to decrease significantly (P less than 0.05) in both patient groups . The administration of DCA to patients during hyperinsulinemia elicited a significant increase in glucose oxidation rate compared with the clamp rate (P less than 0.05), and the percent of glucose uptake oxidized increased from 45.5 +/- 5.5 to 53.5 +/- 4.8%; yet the response of leucine and urea kinetics to the clamp plus DCA was not different from the response to the clamp alone . These results suggest that the maximal effectiveness of insulin to suppress protein breakdown is not impaired and that a deficit in glucose oxidation or energy supply is probably not playing a major role in mediating the protein catabolic response to severe burn injury and sepsis. Am J Physiol, 1989 Sep, 257(3 Pt 1), E301 - 8 Sepsis-induced changes in in vivo insulin action in diabetic rats; Lang CH et al.; The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance . Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli . Basal glucose metabolism was determined with the use of {3-3H}glucose initiated 18 h after the first injection of bacteria . Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique . Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals . Diabetes alone decreased both insulin sensitivity and responsiveness . When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity . Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals . Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals . These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines. Arch Surg, 1989 Sep, 124(9), 1071 - 7 Effect of dichloroacetate on plasma and hepatic amino acids in sterile inflammation and sepsis; Vary TC et al.; The effect of sterile inflammation and chronic sepsis on the plasma and hepatic free amino acid concentrations was determined . Relative to control animals, only minor alterations in the plasma amino acid concentrations were observed in sterile inflammation and sepsis . In liver, concentrations of alanine, serine, threonine, asparagine, proline, and glycine were significantly increased to the same extent in sterile inflammation and sepsis, while hepatic glutamine concentrations were significantly decreased . Compared with sterile inflammation, the branched-chain amino acid concentrations were depressed in the liver of septic animals . Following administration of dichloroacetate, hepatic alanine concentrations were significantly reduced more than threefold in each of the conditions examined; in contrast, significant increases in hepatic concentrations of threonine, glycine, glutamine, glutamate, histidine, and proline were observed . Also following administration of dichloroacetate, the branched-chain amino acid concentrations were all significantly elevated in each of the conditions examined, and plasma alanine concentrations were significantly decreased, while those of glutamine and glycine were significantly increased . These results demonstrate that there is a disassociation between the plasma and hepatic concentration of free amino acids in sterile inflammation and sepsis . Furthermore, the results demonstrate that some of the alterations in hepatic amino acid metabolism may be reversed pharmacologically by dichloroacetate. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1989 Sep-Oct, 30(5), 309 - 15 {Degenerative changes in neutrophils as an indicator of neonatal sepsis}; Peng CT et al.; Detection of the degenerative changes of neutrophils (D.C.N.) including vacuolization and toxic granulation in peripheral blood smear can be of value in identifying neonates with infection . A prospective study of 264 neonates who required septic work-ups in the first month of life was conducted . Thirty neonates were proved to have sepsis subsequently . The accuracy of the degree of the D.C.N . to predict neonatal sepsis was assessed . Vacuolization and/or toxic granulation in neutrophils varied from 0% to over 50%/100 neutrophils scanned . The higher the degree of D.C.N . the greater was the like-hood of sepsis . The positive predictive accuracy and specificity increased with the degree of D.C.N . from 24.7% to 100% and 70% to 100% respectively, but the sensitivity decreased accordingly . When D.C.N . was less than 10% the chance of sepsis was less than 5% . Most of newborns dying of proven sepsis had higher percentage of D.C.N. . These findings suggest that degree of D.C.N . may be associated with the outcome of the patients . This simple test can be performed easily in all hospital; it does not require special laboratory facilities and provide a valuable adjunct in early detection of severity and outcome of the neonates with sepsis. J Pediatr, 1989 Sep, 115(3), 351 - 6 Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis; Dagan R et al.; A prospective study was conducted to determine the frequency and distribution of bacterial and viral pathogens in infants hospitalized with suspected sepsis and to evaluate the potential of virus detection for improving patient management . A causative organism was detected in 157 (67%) of 233 previously healthy infants less than 3 months of age, who had been hospitalized for suspected sepsis: 19 (8%) had bacterial infections, 135 (58%) had viral infections, and 3 (1%) had mixed viral-bacterial infections . Viral infections occurred in a seasonal pattern: enteroviruses were responsible for most of the hospitalizations during summer and fall (65/110; 63%) and respiratory syncytial and influenza A viruses were responsible for most of the infections during winter (44/81; 55%) . In contrast, bacterial infections were not seasonally distributed . Virus was detected in 33% of the 138 infected infants within 24 hours, and in 64% within 3 days . We conclude that viral infections are prevalent among infants hospitalized for suspected sepsis, and most can be detected early enough to influence patient management. Ann Surg, 1989 Sep, 210(3), 297 - 306; discussion 306-7 The influence of fibronectin administration on the incidence of sepsis and septic mortality in severely injured patients . The Medical College of Georgia Fibronectin Research Group; Mansberger AR et al.; Eighty-five trauma patients between the ages of 18 and 55, with American College of Surgeon's (ACOS) trauma scores greater than or equal to 7 were entered into a double-blind, randomized, placebo-controlled study to assess the efficacy of prophylactic fibronectin (Fn) administration on clinical course, sepsis development, and septic mortality . Patients were randomized on admission to receive purified human virus-inactivated Fn or placebo control (human serum albumin, HSA) . Fn or HSA was administered on a daily basis if and when the patient was Fn deficient (less than 75% normal) . When a Fn deficiency was not evident, the patient received saline . Seventy one patients developed Fn deficiencies during their initial clinical course: 36 received Fn, 35 received HSA . Fourteen patients did not develop a Fn deficiency after trauma and thus received only saline . Analysis of admission data demonstrated no significant differences between the three groups with respect to extent of injury (injury severity score, ACOS trauma score) or physiologic assessments of organ function (serum creatinine, bilirubin, lactic acid) . On day 1 after trauma, Fn levels were shown to correlate with other plasma proteins and cellular components (range of r values, 0.24 to 0.75; all p less than 0.05), but not with organ function parameters . Eighteen of 85 patients became septic as judged by clinical criteria . Ten of these patients had received Fn (10 of 36), five had received HSA (5 of 35), and three had received only saline (3 of 14) before the development of sepsis (differences not significant) . When septic, nine of 17 patients developed Fn deficiencies . Six patients received Fn while septic, three received albumin, and eight received saline . Seven patients died: 5 of 6 Fn patients, 1 saline, and 1 HSA recipient . Our data suggest that exogenous Fn repletion in states of deficiency does not alter clinical course, the development of sepsis, or septic mortality. Bol Med Hosp Infant Mex, 1989 Aug, 46(8), 543 - 6 {Usefulness of C-reactive protein for the diagnosis of neonatal sepsis}; Baptista-Gonzalez HA et al.; With the object to determine the utility of C-reactive protein (CRP) in the diagnosis of neonatal sepsis . We proceeded to create the prospective study of cases and controls of newborn included in the study of neonatal sepsis in the Instituto Nacional de Perinatologia . We measured the seric CRP in samples obtained by capillary punction simultaneously with blood culture and/or CSF culture, for bacterial infection criteria . We included 64 newborn divided in two groups: 42 patients were not infected and 22 cases had positive cultures . The results in the uninfected newborn group of CRP were negative to positive dilutions 1:32; with the newborn infected the CRP had values of 1:32 to 1:2048 . The probability to find values equal or major to 1:32 in the infected newborn with positive cultures the CRP have values of sensitivity of 91% and specificity of 93% to get this values . We accept that the CRP could be used systematically for the diagnosis of neonatal sepsis, being a simple procedure and accessible for use in the newborn with sepsis suspicion. South Med J, 1989 Aug, 82(8), 1040 - 3 Fusobacterium necrophorum sepsis with cerebral infarction; Spencer CH et al.; We have described the case of a 23-month-old female child in whom Fusobacterium sepsis progressed to cerebral infarction despite therapy with intravenous chloramphenicol and ampicillin . Some clinical improvement was noted upon addition of metronidazole to the treatment regimen . The child survived, but has severe neurologic sequelae . Physicians should suspect anaerobic infection in children who have signs of severe neurologic infection and in whom cultures are negative for aerobes . In selected cases, early treatment with metronidazole may be helpful. J Trauma, 1989 Aug, 29(8), 1140 - 4; discussion 1144-5 Intra-abdominal sepsis following liver trauma; Bender JS et al.; Of 330 consecutive patients with liver trauma having a celiotomy over a 5-year period, 295 (89%) survived more than 72 hours . Of these 295, 35 (12%) developed sepsis, and 11 (31%) of these septic patients died . The sources of the sepsis in 30 of these patients included: abdominal abscesses--23, pneumonia or empyema--seven, acalculous cholecystitis--two, gangrene of right colon--two, and thigh abscess--one . In five other patients, the source of the sepsis was not found, even at autopsy . The mortality rate in the 30 patients with one or more identifiable foci of infection was 23% . In contrast, when the source of the sepsis could not be found, the mortality rate was 80% (4/5) (p less than 0.05) . Factors associated with an increased incidence of abdominal abscess included: splenectomy, 75% (3/4); liver packs, 63% (5/8); 20+ units of blood, 57% (8/14); Class IV-V liver injury, 35% (8/23); 10-19 units of blood, 25% (7/28); colon injury, 19% (7/36); and open (Penrose) drainage of the abdomen, 11% (23/213) . None of 82 patients without drains developed an intra-abdominal abscess . Thus early control of an identifiable source of infection provides the best results with sepsis following liver trauma . The most effective method for preventing intra-abdominal abscesses appears to be avoidance of drains in mild (Class I-II) liver injuries . The use of a closed system in the most severe injuries is still controversial and needs to be addressed in a prospective trial. Chest, 1989 Aug, 96(2), 363 - 6 Skeletal muscle blood flow and venous capacitance in patients with severe sepsis and systemic hypoperfusion; Astiz ME et al.; Alterations in peripheral vascular tone are presumed to contribute to circulatory failure during severe sepsis . Decreased venous tone with venous pooling may decrease effective circulatory blood volume, while decreased arterial tone with redistribution of systemic blood may compromise tissue nutrient flow . We compared forearm arterial and venous tone and forearm blood flow in ten patients with and ten patients without sepsis . The FVT, MVC, and FBF were measured by air plethysmography . In the septic patients, MCV was 1.4 +/- 0.1 ml compared with 3.1 +/- 0.2 ml in nonseptic patients (p less than 0.01) . The FVT was 13.4 +/- 1.0 mm Hg/ml in septic patients versus 7.0 +/- 0.5 mm Hg/ml in nonseptic patients (p less than 0.01) . The ratio of FBF to cardiac output was 0.28 +/- 0.07 percent in septic patients and 0.31 +/- 0.07 percent in nonseptic patients . These data suggest that increased peripheral venous capacitance and redistribution of skeletal muscle blood flow are not present in patients with sepsis. Surgery, 1989 Aug, 106(2), 156 - 61; discussion 161-2 Prevention and treatment of endotoxin and sepsis lethality with recombinant human tumor necrosis factor; Sheppard BC et al.; Tumor necrosis factor (TNF) is a macrophage product released in response to endotoxin that has been implicated as a cause of the toxicity and lethality seen in septic shock . Previous work suggests that tolerance to nutritional and lethal effects of TNF occur after repeated exposure to recombinant tumor necrosis factor (rTNF) . In this study pretreatment of rats with a single low intravenous dose of rTNF prevented subsequent death when a lethal dose of rTNF was administered 24 hours later (tolerance or tachyphylaxis) . Pretreatment with rTNF also afforded protection against the lethal effects of either endotoxin or cecal ligation and puncture when rats were challenged 24 hours later . Recombinant TNF injected 6 hours after cecal ligation and puncture initially resulted in a significant survival advantage for treated animals . When this experiment was repeated with a different lot of rTNF, however, the therapeutic benefit of rTNF was not obtained until the dose was decreased by a factor of 10 . Protection against the lethal effects of cecal ligation and puncture did not occur when rTNF was given 24 hours after the insult . A single low dose of rTNF can result in tolerance or tachyphylaxis to the lethal effects of TNF . The results suggest that the early administration of low-dose rTNF may be useful in the prevention and treatment of the lethality of sepsis. J Clin Invest, 1989 Aug, 84(2), 443 - 50 Proteolytic inactivation of plasma C1- inhibitor in sepsis; Nuijens JH et al.; Activation of both the complement system and the contact system of intrinsic coagulation is implicated in the pathophysiology of sepsis . Because C1 inhibitor (C1-Inh) regulates the activation of both cascade systems, we studied the characteristics of plasma C1-Inh in 48 patients with severe sepsis on admission to the Intensive Care Unit at the Free University of Amsterdam . The ratio between the level of functional and antigenic C1-Inh (functional index) was significantly reduced in the patients with sepsis compared with healthy volunteers (P = 0.004) . The assessment of modified (cleaved), inactive C1-Inh (iC1-Inh), and complexed forms of C1-Inh (nonfunctional C1-Inh species) revealed that the reduced functional index was mainly due to the presence of iC1-Inh . On SDS-PAGE, iC1-Inh species migrated with a lower apparent molecular weight (Mr 98,000, 91,000, and 86,000) than native C1-Inh (Mr 110,000) . Elevated iC1-Inh levels (greater than or equal to 0.13 microM) were found in 81% of all patients, sometimes up to 1.6 microM . Levels of iC1-Inh on admission appeared to be of prognostic value: iC1-Inh was higher in 27 patients who died than in 21 patients who survived (P = 0.003) . The mortality in 15 patients with iC1-Inh levels up to 0.2 microM was 27%, but in 12 patients with plasma iC1-Inh exceeding 0.44 microM, the mortality was 83% . The overall mortality in the patients with sepsis was 56% . We propose that the cleavage of C1-Inh in patients with sepsis reflects processes that play a major role in the development of fatal complications during sepsis. Crit Care Med, 1989 Aug, 17(8), 724 - 33 Coagulation, fibrinolysis, and kallikrein systems in sepsis: relation to outcome; Hesselvik JF et al.; Fatal multiple organ failure after severe infection may be related to an early activation of protease cascade systems . This study aimed to relate changes in coagulation, fibrinolysis, and kallikrein to shock and outcome . Of 53 patients with severe infection, 30 did not develop shock, 12 survived septic shock, and 11 died from organ failure after septic shock . No patient had overt disseminated intravascular coagulation . We measured 17 components of the coagulation/fibrinolysis/kallikrein pathways on admission and on the next 2 days . High values for fibrinogen, factor VIII:C, von Willebrand factor antigen, and D-dimer were seen in all patients; factor XII, prekallikrein, factor VII, antithrombin, protein C, and fibronectin were low . The patients thus appeared to be hypercoagulable . These disturbances were more pronounced in septic shock survivors, who also had low plasminogen and antiplasmin, indicating ongoing fibrinolysis . Nonsurvivors of sepsis were distinguished mainly by high plasminogen activator inhibitor values; this suggests an impaired functional fibrinolysis in fatal sepsis, with possible therapeutic implications . Cryoprecipitate infusion increased the fibronectin concentration, but did not influence the other factors studied. Anaesthesist, 1989 Jul, 38(7), 379 - 82 {Fulminant sepsis following posttraumatic splenectomy--OPSI (overwhelming postsplenectomy infection) syndrome}; Thoma R et al.; We report a case of fulminant sepsis 10 years after posttraumatic splenectomy . The low-cardiac-output stage of the septic shock with disseminated intravascular coagulation (DIC), which was already marked on admission to the intensive care unit, could not be overcome despite appropriate shock treatment . The pathogenetic spectrum includes more than 70% pneumococci, but any pathogen can trigger an overwhelming postsplenectomy infection (OPSI) syndrome . Pathogenetically, the OPSI syndrome is primarily due to distinctly reduced bacterial clearance from loss of the reticuloendothelial tissue in the spleen . Appropriate treatment of the septic shock is of prime therapeutic importance . In summary, the following recommendations can be made: 1 . Nonspecific symptoms of infection in splenectomized patients, such as fever, call for immediate clarification with respect to the onset of a septic process . Immediate admission to a hospital, close monitoring, including blood cultures, and immediate antibiotic therapy are unavoidable . 2 . The aim of treatment is to prevent DIC by aggressive therapy of the septic shock with prevention of the low-output stage . 3 . Splenectomized patients must be informed of the possibility of a serious, potentially fatal infection and its premonitory symptoms . An emergency passport is appropriate . 4 . In view of the few side effects of the vaccine, all splenectomized patients should be immunized against pneumococci . Children under 2 years of age should furthermore receive prophylactic oral penicillin up to the age of 5. Circ Shock, 1989 Jul, 28(3), 257 - 65 Norepinephrine-induced phosphorylation of a 25 kd phosphoprotein in rat aorta is altered in intraperitoneal sepsis; Carcillo JA et al.; An attenuation of the contractile response to norepinephrine (NE) has been previously demonstrated in rat aorta during intraperitoneal sepsis and endotoxemia . In this study, we determined whether NE-induced protein phosphorylation is altered in septic rat aorta as compared to control rat aorta . We found that the NE-induced phosphorylation of a 25 kd phosphoprotein was decreased . NE increased phosphorylation of the 25 kd band by 54% (P less than .01) in the control aorta but only 12% (not significant) in the septic aorta . Pyrophosphate gel purification of phosphorylated myosin showed that this 25 kd band was not related to the myosin-phosphorylated (P) light chain . Two-dimensional polyacrylamide gel electrophoresis analysis revealed that this 25 kd band represents two proteins with distinct isoelectric points of 6.5 and 6.2 . These results further document that intrinsic alterations occur in the NE-mediated signal transduction system in rat aorta during sepsis and that such alterations could contribute to depressed aortic contractility. Br J Surg, 1989 Jul, 76(7), 687 - 8 Umbilical sepsis; Sroujieh AS et al.; Pilonidal sinus of the umbilicus is rarely reported, and there are only 17 reported cases . On reviewing the records from Jordan University Hospital, 24 patients who were treated surgically for a discharging umbilical sinus were found . Three patients had known causes for their umbilical sepsis, namely stitch sinus, urachal remnant and an umbilical polyp . Of the remaining 21 patients, seven had clinical and pathological evidence of hair in their umbilicus . Most of our patients were young men who presented with discharge, soreness or pain, swelling, and cellulitis . Treatment by umbilical excision, leaving the skin defect to heal by secondary intention, proved satisfactory . The resultant scar resembles a normal umbilicus. Mod Pathol, 1989 Jul, 2(4), 301 - 5 Granulocytic fragments in sepsis; Krauss JS et al.; We report here three patients with sepsis and one with acute pancreatitis and possible sepsis who developed granulocytic fragments on blood smears obtained prior to death . In case 1, these fragments were identified cytochemically . In case 3, granulocytic cytoplasmic projections and fragments were identified by electron microscopy of the buffy coat . All patients had leukerythroblastosis . The average corrected white blood count (WBC) was 46 X 10(9)/liter with 34 nucleated red blood cells (nRBC)/100 WBC . Patient 1 had thrombocytosis whereas patients 2, 3, and 4 were thrombocytopenic . Terminal complement levels were decreased in patients 3 and 4 as previously noted in sepsis (Sprung CL, Shultz DR, Marcial E, et al.: Complement activation in septic shock patients . Crit Care Med 14:525, 1986) . A general correlation between nRBC and granulocytic fragments/100 hpf (high power field) was observed in patients 3 and 4 . Granulocytic fragments were not identified on the blood smears of several patients with leukemoid reactions without erythroblastosis . Although the precise etiology of these fragments is unclear, we believe their recognition is important because all patients died within 32 hours after granulocytic fragments were identified . Furthermore, these fragments can falsely elevate the platelet count . Although myeloid fragments have previously been noted in leukemia and lymphoma, this is the first report of their association with conditions unrelated to hematologic neoplasms . These fragments can easily be recognized by careful examination of the blood smear and represent a newly recognized aspect of the septic shock syndrome. Am Surg, 1989 Jul, 55(7), 462 - 5 The use of ketoconazole in prophylaxis of Candida sepsis; Rietschel P et al.; Candida sepsis has become an increasing problem in ICU patients with up to 50 per cent mortality rate . Ketoconazole, an oral antifungal agent, was used prophylactically in guinea pigs to see if this would prevent Candida sepsis . Absorption of ketoconazole has been stated to increase in an acid environment . Thirty-six guinea pigs were divided into three equal groups: group I received 1 cc normal saline, p.o.; group II received 10 mg/kg ketoconazole dissolved in 1 ml Maalox (Rorer Consumer; Fort Washington, PA); group III received 10 mg/kg ketoconazole in 1 ml in HCl, all given daily . Each animal received 10(8) colony forming units intravenously . The viability of the innoculum was confirmed by culture both pre- and postinjection . Each animal was observed daily for weight and ocular and skin lesions . Half of the animals were sacrificed on day seven and the remaining were sacrificed on day 14 . Cultures, complete blood count (CBC), ketoconazole levels, and specimen histology were obtained . There was no difference between groups as to weight, leukocyte counts, skin or ocular lesions, or ketoconazole levels . Histologic analysis and quantitative cultures revealed little Candida invasion . In conclusion, Candida sepsis cannot be induced in healthy guinea pigs . The blood levels of ketoconazole were not affected by pH. Am Surg, 1989 Jul, 55(7), 450 - 6 Sepsis and antithrombin III, prekallikrein, and fibronectin levels in surgical patients; Wilson RF et al.; Antithrombin (AT), prekallikrein (PK), and fibronectin (FN) were measured in the plasma of 400 patients with a variety of disease states seen at Detroit Receiving Hospital from October 1983 through June 1987 . The average lowest AT measured in these 400 patients was 69 +/- 19 per cent (SD) (Normal = 75-120%) . The average lowest AT level in 152 septic patients (50 +/- 17%) was significantly lower than in the 248 patients without sepsis (79 +/- 22%) (P less than 0.001) . The average lowest PK levels measured in 132 patients was 52 +/- 19 (Normal = 80-120%) . The average PK level in 64 septic patients (34 +/- 17%) was significantly lower than in 68 who were not septic (69 +/- 21%) (P less than 0.001) . The average lowest FN levels measured in 109 patients was 230 +/- 118 mcg/ml (Normal = 200-350 mcg/ml) . The average FN level in 47 septic patients (162 +/- 88 mcg/ml) was significantly lower than in the 62 nonseptic patients (285 +/- 138) mcg/ml . AT or PK levels less than 50 per cent or FN levels less than 150 mcg/ml during the first 24 to 48 hours after severe trauma or burns were associated with a development of later sepsis in 90 per cent, 77 per cent, and 70 per cent, respectively . Thus, low or falling levels of AT, PK, and FN may be of great help in predicting sepsis or providing an early diagnosis in critically ill or injured patients. Surgery, 1989 Jul, 106(1), 87 - 93 Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: results from a preliminary study; Benson DW et al.; Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions . Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known . In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied . Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer . Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes . Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively . Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle . There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation . During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05) . Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle . Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle . The results suggest that calcium uptake and content in skeletal muscle are increased during sepsis and that high calcium concentrations in vitro stimulate nonmyofibrillar protein breakdown . Muscles from septic animals may be more sensitive to the effect of calcium in vitro than muscles from nonseptic rats . Whether increased calcium uptake and content in skeletal muscle is partly responsible for accelerated muscle proteolysis during sepsis remains to be determined. Am J Perinatol, 1989 Jul, 6(3), 356 - 9 Heart rate patterns and fetal sepsis; Youchah J et al.; Fetal heart rate patterns from 15 cases of in utero bacterial fetal sepsis were reviewed . All patterns contained some abnormality, the most common being persistent tachycardia . Ninety-three percent of fetuses had periodic decelerations, which were either late or variable in nature . Neither maternal fever nor fetal tachycardia was invariably present during fetal infection . Although fetal sepsis was associated frequently with fetal heart rate pattern aberrations, no specific pattern was identified that was consistently or uniquely related to infection. ASAIO Trans, 1989 Jul-Sep, 35(3), 343 - 5 Exchange blood transfusion and on-line plasma exchange for sepsis in infants; Asanuma Y et al.; During the last 6 years, 19 infants with sepsis have been treated with exchange blood transfusions 47 times, and 13 patients survived . However, this procedure is compromised by antibody formation against WBCs and platelets . Accordingly, a miniature system for on-line plasma exchange (PE) between septic infant and healthy parent has been developed and evaluated using a canine model . Escherichia coli, at a dose of 5 X 10(9) CFU/ml/kg, was injected intravenously into 17 puppies that were divided into 3 groups; untreated; sham treated; and PE in which 80 ml/kg of plasma in each septic puppy was replaced during 2 hr with fresh plasma simultaneously obtained from healthy adult dogs . Four of 5 puppies survived in the PE group, while all other puppies died within 24 hr . In the PE group, viable cell counts of E . coli and endotoxin decreased significantly, and opsonic activity improved . This system is effective and applicable for treatment of sepsis in infants. Br J Surg, 1989 Jul, 76(7), 752 - 5 Anal endosonography in the evaluation of perianal sepsis and fistula in ano; Law PJ et al.; Anal endosonography has been performed in 22 patients with fistula in ano and perianal sepsis and compared with the operative findings . Using a special hard cone attachment to a radial 7 MHz probe the examination was well tolerated, rapid and generally accurate, detecting two unsuspected foreign bodies and all seven complicated fistula in ano preoperatively. Br J Surg, 1989 Jul, 76(7), 670 - 1 Tumour necrosis factor and bacterial sepsis; Michie HR et al.; This review examines the evidence that tumour necrosis factor is the principal mediator of the derangements associated with severe sepsis. Metabolism, 1989 Jul, 38(7), 634 - 40 Total and myofibrillar protein breakdown in different types of rat skeletal muscle: effects of sepsis and regulation by insulin; Hasselgren PO et al.; Proteolysis is increased in sepsis, but it is not known whether myofibrillar and non-myofibrillar proteins are broken down in the same fashion, or respond to the same regulatory forces as in non-septic muscle . In this study, therefore, the effect of sepsis on total and myofibrillar protein breakdown in incubated rat extensor digitorum longus (EDL) and soleus (SOL) muscles was determined, and the response in vitro to different concentrations of insulin (10 to 10(5) microU/mL) of protein degradation was studied in incubated EDL muscles from control and septic rats . Sepsis was induced in rats weighing 40 to 60 g by cecal ligation and puncture (CLP) . Control animals were sham operated . Sixteen hours after CLP or sham operation, intact EDL and SOL muscles were incubated for two hours in oxygenated Krebs-Henseleit bicarbonate buffer containing glucose (10 mmol/L) and cycloheximide (0.5 mmol/L), and total and myofibrillar protein breakdown was assessed from release into incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively . Tyrosine and 3-MH were determined fluorometrically by high performance liquid chromatography (HPLC) . Tissue levels of tyrosine and 3-MH remained stable both in control and septic muscles during incubation for two hours . The rate of tyrosine release was increased during sepsis by 58% (P less than .001) and 15% (NS) in EDL and SOL muscle, respectively . The corresponding figures for 3-MH were 103% (P less than .001) and 21% (NS) . Tyrosine release was reduced by insulin at a concentration of 10(3) microU/mL in control muscle and at a concentration of 10(4) microU/mL in septic muscle.(ABSTRACT TRUNCATED AT 250 WORDS) Cent Afr J Med, 1989 Jun, 35(6), 410 - 3 Abdominal sepsis: the identification of a high risk subgroup using the APACHE II system in twenty-seven patients; Sleigh JW et al.; The outcome of 27 severely ill patients with intra-abdominal sepsis admitted to I.C.U . was studied . The APACHE II score was done on admission, at 24 hours and at 48 hours . It proved to be an accurate predictor of hospital survival in this group of patients and implications for management are discussed. J Pediatr Surg, 1989 Jun, 24(6), 562 - 6 Surgery, sepsis, and nonspecific immune function in neonates; Madden NP et al.; An audit of 143 neonatal surgical operations identified low birth weight infants as being at particular risk of developing post-operative sepsis following major surgical trauma . Activity of the nonspecific immune system was examined pre- and post-operatively in order to elucidate the susceptibility to post-operative sepsis of these infants . A chemiluminescence micro-method was developed specifically for this purpose . Neonatal plasma was shown to have significantly impaired opsonising activity, and activity was further reduced in low birth weight infants . Levels of immunoglobulin and complement factors were also reduced, particularly in the low birth weight infant . Following major surgical trauma polymorph activity was significantly lower in low birth weight infants than in mature neonates. Surgery, 1989 Jun, 105(6), 747 - 51 The effects of hyperoxia during fulminant sepsis; Garner WL et al.; Although adequate tissue oxygenation is essential to maintain cellular metabolism, the use of hyperoxia to improve oxygen delivery or to improve metabolic performance is controversial . For example, supplemental inspired oxygen is reportedly beneficial in the treatment of some experimental infections; however, oxygen therapy also has well-documented adverse side effects . To evaluate the effect of increased inspired oxygen concentration (FIO2) in animals with fulminant sepsis, 117 Sprague-Dawley rats underwent cecal ligation and puncture . Animals were then exposed to an FIO2 of either 0.21, 0.4, or 0.8 . Twenty sham-operated controls had no mortality with any FIO2 . Increasing the FIO2 increased mortality from 70% to 85% in animals receiving 40% O2, and to 100% in those receiving 80% O2 . Autopsies revealed mild pulmonary oxygen toxicity with 80% O2 exposure in both control and septic animals, but normal lung histologic appearance in animals receiving lower levels of oxygen . Arterial blood gases documented maintenance of oxygenation and ventilation . Thus, pulmonary oxygen toxicity does not appear to be the mechanism for increased mortality . Supplemental oxygen may worsen, rather than improve, survival after fulminant infection. Isr J Med Sci, 1989 Jun, 25(6), 332 - 8 Corticosteroids in sepsis and septic shock: has the jury reached a verdict? Putterman C. Mortality from septic shock remains high, despite early diagnosis, comprehensive care and monitoring, and intensive therapy . The use of high-dose corticosteroids as adjunctive therapy in septic states has been extensively debated in the literature, but no clear consensus has been reached . Main sites of action where corticosteroids can theoretically interfere with the pathophysiologic processes activated by sepsis have been identified . Early clinical studies and extensive animal research generated much enthusiasm for the use of steroids in sepsis and septic shock . Recently, however, well-designed clinical studies have consistently failed to show a beneficial effect of corticosteroid use in septic states . After re-examining the theoretical basis for the use of steroids, possible side effects, experimental results and clinical trials, it is concluded that, based upon current knowledge, high-dose corticosteroids should not be used as adjunctive therapy in human sepsis and septic shock. Circ Shock, 1989 Jun, 28(2), 165 - 78 In vivo insulin resistance during nonlethal hypermetabolic sepsis; Lang CH et al.; The present study was performed to determine whether hypermetabolic sepsis alters peripheral and hepatic insulin sensitivity and/or responsiveness . Nonlethal sepsis was produced in chronically catheterized conscious rats by repeated subcutaneous injections of live Escherichia coli . Basal glucose metabolism was determined using a primed-constant infusion of {3-3H}glucose initiated 20 hr after the first injection of bacteria . Thereafter, in vivo insulin action was assessed using the euglycemic hyperinsulinemic clamp technique . Insulin was infused at various rates in separate groups of animals for 3 hr to produce steady-state insulin levels of approximately 60, 120, 400, 2,500, and 25,000 microU/ml, and euglycemia was maintained by varying the glucose infusion rate . The sepsis-induced hyperglucagonemia was not significantly altered by the infusion of insulin and glucose . In septic rats, the dose-response curve for the insulin-induced increment in glucose utilization was shifted downward and to the right . As a result, septic rats showed a twofold increase in the ED50 value (380 vs . 190 microU/ml) and a 50% reduction in the maximal responsiveness compared with control animals, indicating peripheral insulin resistance . Septic and nonseptic animals, however, had a similar reduction in the endogenous glucose production rate as the plasma insulin concentration was increased, suggesting that there was no hepatic insulin resistance . The plasma lactate concentration increased in a dose-dependent manner in both septic and nonseptic rats as the plasma insulin concentration was raised . However, the increment in steady-state lactate concentration was consistently higher (75-220%) in septic animals at each insulin infusion rate . These results indicate that nonlethal hypermetabolic sepsis in the rat is associated with peripheral insulin resistance. Am J Physiol, 1989 Jun, 256(6 Pt 2), H1524 - 31 Increased lymphatic elimination of interstitial hyaluronan during E . coli sepsis in sheep; Lebel L et al.; The effect of septicemia on the elimination of hyaluronan (HA) from the lung interstitium was investigated in awake sheep with chronic lung lymph and thoracic duct fistulas . The result was compared with that after elevation of left atrial pressure (LAP) . Lymph was sampled before and after a 20-min infusion of Escherichia coli (10(9) bacteria/kg body wt.), after elevation of LAP, or both . Infusion of E . coli caused an increased flux of HA in lung lymph and thoracic duct lymph . After an elevation of LAP, the HA flux in lung lymph was increased to a comparable extent . In animals subjected to an increase in LAP and subsequently to infusion of E . coli, no additive effect on HA flux was seen . The weight-average molecular weight of HA in lung lymph was increased both after sepsis and after elevation of LAP . The findings show that sepsis and elevated transvascular hydrostatic pressure result in increased mobilization of HA from the interstitium . This might partly explain the increased HA concentrations in plasma in clinical sepsis and may also lead to a change in the characteristics of the interstitial matrix in this condition. Acta Paediatr Jpn, 1989 Jun, 31(3), 335 - 9 Histiocytic hemophagocytosis in the bone marrow in children with sepsis and disseminated intravascular coagulation; Hara T et al.; Two children with systemic E . coli and candidial infections developed disseminated intravascular coagulation (DIC) . Bone marrow examination in both cases showed histiocytic hemophagocytosis, consistent with the diagnosis of the hemophagocytic syndrome . Histiocytic hemophagocytosis in the bone marrow, one of the markers of the activated mononuclear phagocyte system, might be common in patients with severe sepsis and DIC, especially in immunodeficiency. Clin Ter, 1989 May 31, 129(4), 287 - 91 {Monotherapy, empirical and targetted, with imipenem-cilastatin in sepsis of bacterial origin}; Fiorentino F et al.; The authors describe an open study in 22 patients with febrile conditions of unknown origin who were treated with imipenem-cilastatin while waiting for routine laboratory and culture tests . These were done immediately at the patients' entry into hospital, after which imipenem-cilastatin treatment was started immediately, and was subsequently confirmed by the isolates and culture tests . The drug was found to be active and to eradicate the responsible organism in all cases . In addition, it was found to be easy to handle and not to give rise to side-effects or changes in laboratory tests. Br J Plast Surg, 1989 May, 42(3), 314 - 7 How does sepsis promote thrombosis in microvascular anastomoses? McLean NR, Ellis H. This study on 100 rats, divided into five equal groups, has shown that chronic distant sepsis promotes occlusion of microvascular anastomoses to a significantly greater extent than aseptic inflammation, transient bacteraemia and even local infection . This may be related to the significant increase in the number of platelets in the group with distant sepsis. APMIS, 1989 May, 97(5), 441 - 6 Dysfunction of the mononuclear phagocytic system in sepsis; Gutierrez-Fernandez J et al.; An in vivo study has been undertaken of the Fc(IgG) receptor-mediated phagocytic capacity of macrophages (clearance of anti-rhesus D-coated-51 Cr-labelled autologous erythrocytes, expressed as half-lives) in 15 cases of sepsis to establish its behaviour and correlate this function to levels of circulating immune complexes (anti-Clq-nephelometry) . Five patients with low activity (2261 +/- 859 minutes) developed septic shock; the other ten showed high activity (5.8 +/- 1.5 minutes) and did not develop septic shock . Differences from the control group (30 +/- 12 minutes) were found (p less than 0.001) . Receptor activity was related to the presence of circulating immune complexes (p less than or equal to 0.001; delta = 0.862) but not to age, sex, or the presence/absence of splenomegaly during the illness . Eight patients responded favourably; seven patients died; but the receptor activity was not related to this . During sepsis it is possible to find higher Fc(IgG) receptor-mediated phagocytic capacity of macrophages . Excessive formation of circulating immune complexes has a negative influence on Fc(IgG) receptor-mediated phagocytosis . This activity of macrophages, measured at the start of the sepsis, was not associated with the final outcome of the patients' illness (cure or death). Crit Care Med, 1989 May, 17(5), 399 - 403 Cerebral blood flow is reduced in patients with sepsis syndrome; Bowton DL et al.; The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship . We measured CBF and cerebrovascular reactivity to CO2 in nine patients with sepsis syndrome using the 133Xe clearance technique . Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02) . This depression did not correlate with changes in mean arterial pressure . Despite the reduction in CBF, the specific reactivity of the cerebral vasculature to changes in CO2 was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg . Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study. Crit Care Med, 1989 May, 17(5), 394 - 8 Effects of pentastarch and albumin infusion on cardiorespiratory function and coagulation in patients with severe sepsis and systemic hypoperfusion; Rackow EC et al.; Twenty consecutive patients with severe sepsis were randomized to fluid challenge with 5% albumin or 10% low MW hydroxyethyl starch (pentastarch) solutions . Fluid challenge was administered iv as 250 ml of test colloid every 15 min until the pulmonary artery wedge pressure (WP) was greater than or equal to 15 mm Hg or a maximum dose of 2000 ml was infused . Hemodynamic, respiratory, and coagulation profiles were measured before and after fluid infusion . The amount of colloid required to achieve a WP of 15 mm Hg was comparable between groups . Both colloid infusions resulted in similar increases in cardiac output, stroke output, and stroke work . The effect of fluid infusion with pentastarch on coagulation was not significantly different from albumin, although pentastarch was associated with a 45% decrease in factor VIII:c . We conclude that pentastarch is equivalent to albumin for fluid resuscitation of patients with severe sepsis. Crit Care Med, 1989 Apr, 17(4), 323 - 7 Left ventricular function during sepsis; Artucio H et al.; The prevalence and prognostic significance of left ventricular involvement in septic patients without shock was investigated . Systolic time intervals (STI) and preejection period/left ventricular ejection time ratio (PEP/LVET) were used to assess left ventricular function . Forty-nine patients, 22 of whom ultimately died, were studied . The group as a whole showed abnormal PEP/LVET ratio (0.40 +/- 0.02) that differed significantly (p less than .01) from reported normal values (0.345 +/- 0.002), demonstrating widespread left ventricular dysfunction in this population . In order to establish the prognostic significance of left ventricular impairment, the population was divided into two groups according to the PEP/LVET ratio . Group 1 (PEP/LVET less than or equal to 0.42) showed a mortality rate of 10/33 (30%), while group 2 (PEP/LVET greater than 0.42) had a significantly greater mortality (12/16 {75%}, p less than .001) . The test that has a sensitivity of 55%, a specificity of 85%, and a positive predictive value of 75% identifies a subset of septic patients with severe impairment of left ventricular function and high risk of dying. Rev Med Chil, 1989 Apr, 117(4), 385 - 91 {Role of the liver in septic encephalopathy . A disorder associated with multiple organ failure caused by sepsis}; Videla C et al.; The appearance of jaundice during a septic process is usually associated to multiple organ failure and a high mortality rate . Among 17 septic patients followed prospectively, we found 11 with hepatic dysfunction . Abnormal levels of bilirubin and alanine-aminotransferase were found . Glutamine concentration in spinal fluid was 26 +/- 19.4 mg/dl vs 9.43 +/- 2.41 in patients without liver failure (p less than 0.05) . Significant correlations were found among levels of bilirubin and glutamine (r = 0.83), creatinine (r = 0.708), number of platelets (r = 0.778) and between glutamine and creatinine (r = 0.708) . Patients with liver failure presented a higher rate of renal failure and thrombocytopenia (p less than 0.01) and a higher mortality rate . These findings confirm that liver failure is associated to multiple organ failure and thrombocytopenia . It may be related to small vessel occlusion. Br J Surg, 1989 Apr, 76(4), 374 - 7 Relationship between bile colonization, high-risk factors and postoperative sepsis in patients undergoing biliary tract operations while receiving a prophylactic antibiotic . West of Scotland Surgical Infection Study Group; Wells GR et al.; A prospective audit of 644 patients undergoing biliary tract operations has been conducted to assess the incidence of bile colonization and its association with the incidence of postoperative sepsis when all patients received the same prophylactic antibiotic . The accuracy of the determination of high-risk factors has been assessed as has the correlation between bile colonization and patients assessed as 'high risk' . Organisms were cultured from the bile of 121 (19 per cent) patients and among these the incidence of wound or intra-abdominal sepsis was 22 per cent whereas among patients with sterile bile the incidence was only 2 per cent (P less than 0.0001) . Although the incidence of bile colonization within the high-risk group (32 per cent) was more than twice that in the low-risk group (14 per cent), more than half (54 per cent) of the patients with positive bile cultures were in the low-risk group . It is concluded that, despite prophylactic antibiotics, bile colonization remains the major factor associated with postoperative sepsis, but that this cannot be predicted accurately by preoperative assessment of high-risk factors . Furthermore, we believe that a policy of selective administration of prophylactic antibiotics solely to high-risk patients cannot be justified. Am J Obstet Gynecol, 1989 Mar, 160(3), 573 - 4 Gonococcal chorioamnionitis associated with sepsis: a case report; Smith LG Jr et al.; We present a case of gonococcal chorioamnionitis in a patient with intact membranes, which has not been previously reported . Evidence suggests that the spread of bacteria was transplacental. Am Rev Respir Dis, 1989 Mar, 139(3), 674 - 81 The effects of prostaglandin E1 on lung injury complicating hyperdynamic sepsis in sheep; Sibbald WJ et al.; We examined the hypothesis that PGE1 would reduce the severity of lung injury in sheep rendered septic by cecal ligation and perforation (CLP) . Twenty-four to 30 h after CLP, septic lung injury was documented in 37 sheep because pulmonary lymph flow (Qlym) was increased above the baseline, nonseptic study (delta = +7.38 +/- 5.1 ml/h; p less than 0.05), whereas the lymph-to-plasma total protein ratios remained unchanged . During a subsequent 24-h "septic treatment" study period, Qlym continued to increase in an untreated study group (septic treatment minus septic delta = +10.24 +/- 4.9 ml/h; p less than 0.05), but not in sheep treated with PGE1 by continuous infusion at two doses, 1 micrograms/kg/h ("low-dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS) and 1 microgram/kg/min ("high-dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS . Mean pulmonary artery pressures (Ppa) increased in the untreated group during the septic treatment period (delta = +3.74 +/- 4.8 mm Hg; p less than 0.01), but not during PGE1 infusion in either of the low-dose (delta Ppa = -4.1 +/- 5.7 mm Hg; p less than 0.04) or the high-dose (delta Ppa = -0.1 +/- 6.2 mm Hg; P = NS) groups . Unlike other study groups, the PaO2 fell in the high-dose PGE1 group during the septic treatment study (delta PaO2 = -15.0 +/- 9.6 mm Hg; p less than 0.01) . During a study period of drug withdrawal 24 h after the septic-treatment period, Qlym again increased in the low-dose PGE1 group such that the untreated and PGE1 groups were no longer dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS) Dis Colon Rectum, 1989 Mar, 32(3), 219 - 22 Intraoperative colonic irrigation with povidone iodine . An effective method of wound sepsis prevention; Banich FE et al.; In the ten-year period between 1975 and 1986, 367 patients underwent colonic resection with subsequent anastomosis using intraoperative colonic irrigation with 10 percent povidone iodine . One hundred thirty three patients underwent resection of the right or transverse colon, whereas 233 patients had left hemicolectomy with low anterior anastomosis or reanatomosis . Twenty individuals underwent emergency resection for perforation and temporary end colostomy . Nineteen of these patients returned for definitive reanastomosis as part of a two-stage procedure . The rate of wound infection, and/or intra-abdominal abscess formation was retrospectively reviewed and found to be completely nonexistent in these patients . This study examines the various techniques used to reduce the rate of wound infection after colonic surgery and addresses the concept of intraoperative povidone iodine irrigation. Chest, 1989 Mar, 95(3), 612 - 5 Inotropic response to digoxin and dopamine in patients with severe sepsis, cardiac failure, and systemic hypoperfusion; Nasraway SA et al.; We studied the inotropic response to dopamine and digoxin in 20 patients with severe sepsis and left ventricular failure . Left ventricular failure was defined as a left ventricular stroke work index less than or equal to 40 g.m/m2 at a pulmonary artery wedge pressure greater than or equal to 15 mm Hg . Hemodynamic assessment was obtained before and following administration of digoxin 10 micrograms/kg IV or dopamine, 5 to 12 micrograms/kg/min IV . Patients treated with digoxin demonstrated a significant increase in LVSWI . The LVSWI increased 13 +/- 10 percent in the dopamine-treated patients compared with 74 +/- 16 percent in the digoxin patients (p less than 0.02) . We conclude that digoxin exhibited significant inotropic activity in patients with sepsis. Nippon Geka Gakkai Zasshi, 1989 Mar, 90(3), 334 - 42 {Polymorphonuclear leukocyte elastase (PMNE) levels in sepsis; the effect of PMNE on multiple organ failure (MOF)}; Tanaka H et al.; To study the role of lysosomal protease released from polymorphonuclear leukocytes during MOF, plasma PMNE levels were measured serially in 38 patients . The patients were divided into two groups, 14 patients of MOF from sepsis (group 1), and 24 injured patients without MOF (group 2) . The normal value of PMNE was from 21 to 165 micrograms/l . The PMNE levels of the group 1 elevated (831 +/- 241 micrograms/l) at the time of diagnosis of sepsis and remained high during MOF . On the contrary, those of the group 2 were high on admission (574 +/- 131 micrograms/l), but returned to normal within seven days . There was no relationship between the levels of PMNE and the number of neutrophils . However, the PMNE/neutrophils ratio was significantly higher in group 1 . Correlations were demonstrated between the amount of PMNE and the decrease in the levels of platelet counts, fibronectin and coagulation factor XIII . It is suggested that PMNE might play a major role in the pathobiochemical changes and tissue injury during MOF. Acta Chir Belg, 1989 Mar-Apr, 89(2), 77 - 81 {Treatment of intra-abdominal sepsis and necrotizing pancreatitis with staged lavage using a Zipper}; Vermassen F et al.; The mortality of generalised intra-abdominal sepsis and severe necrotising pancreatitis remains very high . The persistence of intra-abdominal septic foci leads to recurrent abscess formation, persistence of sepsis and development of multiple organ failure, ultimately leading to the death of the patient . Therefore we believe that a repeated and total elimination of all septic and necrotic material is the cornerstone of an adequate surgical therapy in these patients . We performed "staged lavage" with the aid of a Zipper in 24 patients (10 with intra-abdominal sepsis and 14 with severe necrotising pancreatitis) . Via the Zipper 98 relaparotomies were performed (mean 4.1 per patient) . The high Apache II-scores (12 to 45, mean 24) illustrate the severity of disease in most of these patients . The expected in-hospital mortality-rate was 59% while in our series 7 patients died on a total of 24 (28%). Rozhl Chir, 1989 Mar, 68(3), 180 - 4 {Appendicitis and anaerobic sepsis}; Vanko D et al.; The paper deals with the treacherous character of acute abdominal attacks of appendical origin complicated by anaerobic sepsis, based on an analysis of 255 patients incl . 57 patients with positive anaerobic cultivations (35.08%), with the number of surgical revisions (36.84%) where patients were reoperated several times, and the impact on medical and economic problems. Head Neck, 1989 Mar-Apr, 11(2), 164 - 9 Postanginal sepsis; Shapiro J et al.; Postanginal sepsis is a septicemia resulting from an antecedent pharyngitis that causes an internal jugular vein thrombophlebitis . Because of the severity of the disease and the difficulty in its diagnosis, familiarity with all aspects of the disease is essential . We present three cases and review the literature on postanginal sepsis . The clinical course of the disease is described and its evaluation and treatment are outlined. G Chir, 1989 Mar, 10(3), 81 - 7 {Surgical sepsis: myths and realities}; De Salvo L et al.; The authors review the modern knowledge of sepsis, asepsis and antisepsis in surgery; they underline some surgeon's customary attitudes and convictions no more scientifically significant today. Eur J Clin Microbiol Infect Dis, 1989 Mar, 8(3), 241 - 4 Randomized trial using piperacillin versus ampicillin and amikacin for treatment of premature neonates with risk factors for sepsis; Hammerberg O et al.; Premature infants with risk factors for early onset sepsis who were less than seven days of age were blindly randomized to receive either piperacillin and placebo (200 infants) or ampicillin and amikacin (196 infants) . One of 30 treated infants developed positive blood cultures . The overall mortality in the two groups was 8.5% for piperacillin/placebo and 13.8% for ampicillin/amikacin (p = 0.11) . Serum creatinine elevation above 100 mumol/l (1.131 mg/dl) during treatment was similar in the two groups . The effectiveness of piperacillin/placebo is similar to that of ampicillin/amikacin for empiric treatment of premature newborns with risk factors for early onset sepsis. JPEN J Parenter Enteral Nutr, 1989 Mar-Apr, 13(2), 141 - 6 Impact of fat and glucose administration on metabolic and respiratory interactions in sepsis; Giovannini I et al.; Metabolic and respiratory interactions were analyzed in a large group of septic patients (S) and in a reference group of nonseptics (NS) during the iv administration of glucose and fat . In spite of a moderate increase in CO2 production (VCO2) observed during the administration of fat in S, a VCO2-sparing effect of fat, with respect to equicaloric amounts of glucose, was reconfirmed . The relevance of the therapeutic modulation of CO2 production during parenteral nutrition, and the relative impact on the abnormal septic respiratory patterns, were emphasized by analyzing the physiological relationships and mechanisms responsible for the increase in respiratory work in sepsis. Arch Surg, 1989 Mar, 124(3), 362 - 72 Determinants of urea nitrogen production in sepsis . Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids; Pittiruti M et al.; The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies) . The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool . While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001) . Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function . The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group . At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients . These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs . In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs. Klin Wochenschr, 1989 Feb 1, 67(3), 207 - 11 Phospholipase A--a parameter of sepsis? A comparison of PLA and Stevens' Sepsis Severity Score; Schild A et al.; Phospholipase A (PLA) and Sepsis Severity Score (SSS) were measured regularly in 28 patients with sepsis (n = 11), pancreatic operations (n = 7), or multitrauma combined with contused abdominal trauma (n = 10) . No linear correlation was found between these two parameters . A statistical correlation could be shown for the paired values PLAmax/SSS or PLA/SSSmax . They lie together above or below their "critical value" of 20 points SSS or 30 U/l PLA (alpha less than 0.05) . The evaluation of mortality shows a distinctly higher significance for the SSS (P less than 0.01) in comparison with the PLA (P less than 0.05) . In certain cases PLA was the first parameter which could have shown the beginning of a septic process. J Trauma, 1989 Feb, 29(2), 152 - 7 Predicting the outcome of exploratory laparotomy in ICU patients with sepsis or organ failure; Sutherland FR et al.; Critically ill patients with sepsis and/or organ failure are difficult to assess . They are often comatose or on steroids and many nonspecific findings such as fever, positive blood cultures, or septic shock which may suggest intra-abdominal sepsis are far from diagnostic . To determine whether decision making regarding the use of laparotomy in these patients could be improved upon, we reviewed our experience with consecutive intensive care unit patients who had laparotomy and we related laparotomy outcome to clinical signs and symptoms . Seventy-three per cent of the 100 laparotomies reviewed were positive for intra-abdominal sepsis . A discriminant function analysis revealed that eight factors in combination predicted laparotomy outcome . However, the overall accuracy of the discriminant function prediction (76.8%) offered little improvement over the policy in place for performing laparotomies in this group of patients at the participating hospitals during the time period of our investigation. Surg Gynecol Obstet, 1989 Feb, 168(2), 148 - 56 Hemodynamic and metabolic alterations during experimental sepsis in young and adult rats; Pedersen PV et al.; Cecal ligation and puncture (CLP) has been extensively used as a model of sepsis in adult rats . It is not known if the response to sepsis is similar in young and adult rats . This investigation was done to compare hemodynamic and metabolic alterations in young (four to six weeks of age, 60 to 90 grams) and adult (12 to 14 weeks of age, 270 to 340 grams) rats after CLP . In one series of experiments, survival rate was determined for 96 hours, and in other experiments, mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), blood and peritoneal cultures and resting energy expenditure (REE) were determined eight and 16 hours after CLP . Levels of glycogen in liver and muscle were determined 16 hours after CLP . Mortality rate was similar in young and adult rats . MAP was stable throughout the course of sepsis, with no significant differences between the two groups of rats . HR was higher in young rats at all times studied . The adult rats became hyperglycemic after CLP while the young were hypoglycemic eight hours after CLP but normalized at 16 hours . Plasma lactate and BUN were similar in the two groups of rats, and no alterations were seen during sepsis . Both young and adult rats became hypoaminoacidemic after CLP . The phenylalanine to tyrosine ratio increased in a similar manner during sepsis in both experimental groups . REE was higher in young than in adult rats, but no significant changes were observed during the course of sepsis in either group.(ABSTRACT TRUNCATED AT 250 WORDS) Klin Wochenschr, 1989 Feb 1, 67(3), 190 - 5 Phospholipase A in acute lung injury after trauma and sepsis: its relation to the inflammatory mediators PMN-elastase, C3a, and neopterin; Kellermann W et al.; Inflammatory mediators involved in the pathogenesis of the adult respiratory distress syndrome (ARDS) are products of the humeral cascade systems like the complement cascade and substances released from neutrophil granulocytes and macrophages like proteases, O2-radicals and arachidonate products . Phospholipase A2 (PLA) was shown by Vadas et al . to be correlated with circulatory shock in the sepsis syndrome, the probably most important underlying disease of ARDS . In a clinical study in 48 patients at risk for ARDS after trauma and sepsis we found plasma PLA elevated (52 +/- 5 U/l) in sepsis, with a positive correlation to the complement split product C3a (r = 0.42, p less than 0.01) and neopterin (r = 0.49, p less than 0.05), which serves as a marker of macrophage stimulation . Elastase-alpha 1PI and C3a showed higher plasma levels in patients with ARDS compared with non-ARDS patients, whereas the neopterin and PLA concentrations were not different with regard to ARDS . The relation between PLA and neopterin shown in the study is consistent with the possibility of macrophages being a source of the plasma PLA, as reported in experimental studies. Indian Pediatr, 1989 Feb, 26(2), 156 - 60 Simple hematological tests for diagnosis of neonatal sepsis; Misra PK et al.; Simple hematological tests, TLC, DLC, mESR, platelet count, were performed in 128 neonates of which 50 were controls and 78 were cases of suspected septicemia . Thirty three had positive blood cultures and were taken as 'proved' and remaining as 'probable' sepsis . A band cell neutrophil (B/N) ratio of greater than 0.2 was most sensitive index (92%) followed by raised mESR of greater than 8 mm for 1st hour, whereas leukopenia of greater than 5 x 10(3)/mm3 was most specific index (88%) for the diagnosis of sepsis . Thrombocytopenia of less than 1.5 x 10(5)/cu mm was also taken as positive test for sepsis . A combination of three positive tests had highest positive predictive accuracy (94%) for early diagnosis of sepsis, when compared to single test or two positive test combinations . The best combination of tests was B/N ratio, leukopenia and mESR which can be easily done in a side laboratory. Br J Surg, 1989 Feb, 76(2), 161 - 4 Reticuloendothelial failure in chronic intra-abdominal sepsis: the role of opsonic fibronectin; Cheslyn-Curtis S et al.; Severe sepsis leads to depression of the reticuloendothelial (RE) system with delayed bloodstream clearance of particulate matter and bacteria . Fibronectin may be an important opsonin of the RE system and low fibronectin levels often accompany severe sepsis in man . We have investigated the effect of prolonged intra-abdominal sepsis on plasma fibronectin concentrations and RE function . Serial plasma fibronectin concentrations were determined in rabbits for 2 weeks after either the induction of sepsis (appendix abscess) (n = 6) or laparotomy only (n = 6) . RE function was measured at 2 weeks by determining the clearance kinetics and organ distribution of low dose technetium tin colloid (TTC) . There was an early transient depression in plasma fibronectin values followed by elevated concentrations at 48-72 h which were more marked in the sepsis group . There was a delay in the blood clearance with reduced hepatic and increased bone uptake of TTC . We conclude that depletion of opsonic fibronectin is unlikely to be an important factor contributing to the impairment of RE function associated with intra-abdominal sepsis and that RE depression in septic animals is due to intrinsic Kupffer cell dysfunction. J R Coll Surg Edinb, 1989 Feb, 34(1), 1 - 8 Critical abdominal sepsis; Rogers PN et al.; Intra-abdominal sepsis is a heterogeneous condition which in its severe forms carries a high mortality . The systemic consequences of established major infection are the result of a complex pathophysiology whose mechanisms are imcompletely understood . It is clear that early appropriate therapy is vital in minimizing effects of intra-abdominal infection and to this end early recognition of sepsis is important . Clinical examination may be unhelpful in difficult cases and special investigations may aid diagnosis; a high index of suspicion is mandatory . Surgery is the mainstay of therapy but may be inadequate and supportive measures are an essential adjunct. Helv Paediatr Acta, 1989 Feb, 43(4), 283 - 94 The use of intravenous gamma-globulin for prevention of sepsis in pre-term infants . A controlled clinical trial; Didato MA et al.; This paper reports a randomized clinical trial to study the effect of an intravenous gamma-globulin preparation to prevent sepsis in pre-term newborn infants . 80 infants were enrolled: 37 of birthweight less than or equal to 1500 g and 43 of birthweight 1501-2000 g . In each group 20 infants received an intravenous preparation of gamma-globulin (0.5 g/kg/wk); the remaining 17 and 20, respectively, served as control cases . No significant differences in the occurrence of sepsis were observed between the group receiving prophylactively intravenous gamma-globulin and the control group . This is particularly evident in infants under intensive care (35% of the total population): in this group 2/3 of sepsis occurred in infants who received IgG . Among the infants with sepsis, the presence of an umbilical artery catheterization represented a significant risk-factor . The post-dose increment of serum IgG did not differ significantly in infants with and without sepsis; the post-dose serum disappearance rate in concentration appears identical in the two groups. Br J Surg, 1989 Feb, 76(2), 115 - 22 Metabolic response to sepsis and trauma; Douglas RG et al.; This review examines current knowledge regarding the metabolic responses to trauma and sepsis . The factors which may mediate the responses are discussed and the potential value of pharmacological or nutritional manipulation is reviewed. Eur J Clin Microbiol Infect Dis, 1989 Feb, 8(2), 142 - 4 Evaluation of central venous catheter sepsis by differential quantitative blood culture; Fan ST et al.; The accuracy of differential quantitative blood culture in the diagnosis of central venous catheter sepsis was evaluated in 24 parenterally-fed patients in whom catheter sepsis was suspected . The pour-plate quantitative culture technique was performed immediately before removal of the catheter on blood drawn through the central venous catheter and a peripheral vein . If bacterial colonies in the catheter blood specimen were sevenfold more frequent than identical bacterial colonies in the peripheral blood specimen, the test was considered positive and indicative of catheter sepsis . Catheter-tip culture identified 9 of the 24 patients as positive for catheter sepsis . A positive differential quantitative blood culture result was found for seven of the nine infected catheters . Sensitivity of this test was 77.8%, specificity was 100%, and overall accuracy was 91.7% . It is concluded that differential quantitative blood culture is a reliable method for the exclusion of catheter sepsis. J Surg Res, 1989 Feb, 46(2), 118 - 22 Hyper and hypodynamic models of sepsis in guinea pigs; Durkot MJ et al.; The acute metabolic response following experimentally induced sepsis can generally be classified as either hypodynamic ("low flow") or hyperdynamic ("high flow") . We have found that in conscious guinea pigs the bolus infusion of 10(10) live Escherichia coli bacteria can elicit either response, depending on the route of administration of the bacteria . Intravenous infusion results in the hypodynamic condition of septic shock in which oxygen consumption (VO2) is reduced to approximately 60% of the control level, plasma glucose is elevated 4 hr after infusion with a reversal to extreme hypoglycemia 12 hr after infusion, and body temperature is reduced by approximately 5 degrees C in 12 hr . In contrast, subcutaneous injection results in increased VO2, body temperature, and plasma glucose . In both models the concentration of cortisol, catecholamines and glucagon were elevated, but the responses were more pronounced in the hypodynamic model . In both cases, insulin concentration was decreased . These models of sepsis are useful because many aspects of response are comparable to man, they are simple to create, and they are consistent and reproducible. Zentralbl Chir, 1989, 114(2), 114 - 20 The anergic state as a predictor of pancreatic sepsis; Garcia-Sabrido JL et al.; From 1984 to 1987, 187 patients with acute pancreatitis (AP) were studied . All patients were stratified according to Ranson's criteria upon admission and were followed up by performing a CT scan weekly . One hundred and thirty-eight patients had 3 or less Ranson's criteria (non-severe acute pancreatitis = NSAP) and 49 presented 4 or more (severe acute pancreatitis = SAP) . Ninety-six percent of the patients with (p less than 0.0001) . Of the 49 patients with SAP, 39 developed pancreatic or peripancreatic NSAP were reactive to skin tests on the third week, while 4% remained anergic necrosis and were operated . Twenty-two of these patients had positive cultures demonstrating the presence of bacteria in the tissue samples . One hundred percent of the infected patients remained anergic until surgery, while only 40% of those with negative cultures remained anergic (p less than 0.05) . Mortality rate correlated well with skin test responses, being 31% in anergic patients while only 5% in reactive subjects . Sustained anergic state (AS), sequentially checked, is associated with a high incidence of pancreatic sepsis. Am Surg, 1989 Jan, 55(1), 50 - 4 Gastrointestinal disconnection and the treatment of intra-abdominal sepsis; Schwartz RW et al.; Current operative treatment for intra-abdominal sepsis secondary to internal gastrointestinal fistulas is aimed at wide drainage of septic foci and elimination of continued peritoneal soilage . Although methods for surgical drainage of abscesses and fistulous tracts are well established, the optimal method for surgical prevention of continued peritoneal soilage remains controversial . The authors applied the principle of complete gastrointestinal disconnection and performed diversion of the gastrointestinal tract and tube decompression proximal to the fistulous opening in the treatment of 22 critically ill patients with intra-abdominal sepsis from gastric or small bowel fistulas . Patient survival varied according to the level of the site of gastrointestinal leakage . All patients (5 out of 5) who had leakage in the distal small bowel survived . Six of nine (66%) patients with leakage from the proximal jejunum and six of eight (75%) of patients with gastroduodenal leakage survived . The overall survival rate of 77 per cent observed in this group of patients supports the authors' hypothesis that complete gastrointestinal disconnection is a valuable adjunct in the treatment of these severely ill patients. Ann Surg, 1989 Jan, 209(1), 57 - 62 Plasma-amino acid profiles in sepsis and stress; Vente JP et al.; Sepsis has been associated with specific plasma amino acid patterns . Sixty-five patients were prospectively investigated as to whether these patterns are indeed sepsis specific, or specific for metabolic stress without concomitant sepsis, or associated with the presence of organ failure . Virtually all aminoacid levels were decreased by 10-30% (p less than 0.05), whereas cystine and phenylalanine were significantly elevated . These changes were more pronounced in severe sepsis . Organ failure was not associated with significantly altered amino acid profiles . No differences were found between sepsis and stress without signs of sepsis . In addition, imminent death was not associated with aberrant amino acid profiles . We conclude that sepsis and metabolic stress are associated with changes in plasma amino acid profiles, but that such changes are aspecific and therefore poor indicators of disease severity. Am J Med, 1989 Jan, 86(1), 20 - 6 Elevated plasma levels of the anaphylatoxins C3a and C4a are associated with a fatal outcome in sepsis; Hack CE et al.; PURPOSE AND PATIENTS AND METHODS: Both complement and contact system of coagulation have been implicated in the pathophysiology of sepsis . We therefore measured levels of the complement activation products C1-C1-inhibitor complexes and C3a in serial plasma samples (obtained every six hours) from 48 patients with clinically suspected sepsis, and related these levels to the clinical outcome . C4a was also measured in samples obtained on admission . RESULTS: C3a levels were elevated in 47 patients at least once during the observation period . These levels appeared to be considerably higher in patients who died than in patients who survived . This difference was found for the levels on admission (p = 0.0003), as well as for the highest (p = 0.0010) and the lowest (p less than 0.0001) levels encountered in each patient . The mortality in patients with plasma C3a levels of 13 nmol/liter or less on admission (27 patients) was 33 percent, compared with 86 percent in patients with levels of 14 nmol/liter or more . Patients with septic shock had significantly higher C3a levels than normotensive patients (p values between 0.046 and 0.004) . No significant differences in C3a were found between patients who had respiratory distress syndrome and those who did not . C4a levels in plasma samples obtained on admission were elevated in 43 patients . These levels correlated very significantly with C3a levels (p less than 0.0001), and showed similar associations with a fatal outcome . C1-C1-inhibitor complexes were elevated in 23 patients at least once during the observation period . These patients had significantly higher levels of C4a and C3a than patients with normal amounts of C1-C1-inhibitor complexes . Patients who died had higher levels of C1-C1-inhibitor complexes than patients who survived . However, this difference was not significant . CONCLUSION: On the basis of our results, we propose that activation of the complement system via the classical pathway is involved in the development of fatal complications in sepsis. Prog Clin Biol Res, 1989, 308, 719 - 24 The prognostic value of plasmaproteins in patients with abdominal sepsis; Rogy M et al.; In the course of the history of patients with severe peritonitis, opsonins, complements and other proteins of the plasma showed no significant difference between the data of the patients who later died or survived . We conclude that simple parameters like platelet count, creatinine and respiratory function are more sufficient. Indian Pediatr, 1989 Jan, 26(1), 26 - 31 Hemostatic changes in neonates with anoxia and sepsis; Dube B et al.; Hemostatic profile (prothrombin time (PT), thrombin time (TT), kaolin cephalin clotting time (KCCT), plasma fibrinogen, serum fibrin/fibrinogen degradation products (FDP) and platelet counts) was examined in 153 neonates with birth anoxia and 86 with sepsis . Remarkable hemostatic alterations occurred in neonates with severe anoxia and sepsis, while those with moderate anoxia exhibited minimal or no change . Vitamin K administration to anoxic babies showed no improvement in the hemostatic profile after 48-72 hours . The hemostatic alterations were presumably due to incipient disseminated intravascular coagulation (DIC) . In spite of the marked coagulation changes, only 3 neonates with sepsis and none of the anoxic newborns presented with clinical bleeding indicating a well balanced hemostatic mechanism. Int J Biochem, 1989, 21(4), 419 - 23 Skeletal muscle glutamine metabolism during sepsis in the rat; Parry-Billings M et al.; 1 . The effect of sepsis, induced by caecal ligation plus puncture (CLP) or endotoxin injection, on glutamine metabolism was studied in rat skeletal muscle . 2 . The concentration of glutamine in muscle was d