The systemic inflammatory response to cardiopulmonary bypass and the brain

The acquired immune deficiency syndrome (AIDS) is a lethal multisystem disease. Its ocular manifestations have received relatively little attention in the literature. Between 73% and 100% of AIDS patients develop ocular lesions. The commonest lesions seen are retinal--either infectious or noninfectious retinopathy. Involvement of the conjunctiva with Kaposi's sarcoma, infected tears and infected cornea as well as the vitreous are less common. Infections with cytomegalovirus and varicella zoster virus are common causes of visual loss and can be treated with antiviral agents such as ganciclovir and foscarnet. This greatly increases the quality of life in these patients by preventing visual loss.     

Relative contribution of endothelial cell and polymorphonuclear neutrophil activation in their interactions in systemic inflammatory response syndrome

OBJECTIVE: To examine the relative contribution of polymorphonuclear neutrophil (PMN) vs endothelial cell (EC) activation on the adherence and subsequent killing of ECs by PMNs. DESIGN: In vitro comparative studies of PMN-EC adherence and cytotoxicity. SETTING: Research laboratory and the surgical intensive care unit of a tertiary-level university hospital. PATIENTS: Patients with systemic inflammatory response syndrome admitted to the surgical intensive care unit and hospitalized preoperative noninfected surgical patients. INTERVENTION: None. METHODS: Polymorphonuclear neutrophils were isolated from 21 healthy volunteers, 22 preoperative patients, and 30 patients from the surgical intensive care unit with systemic inflammatory response syndrome. The PMNs were activated with lipopolysaccharide, 100 ng/mL (Escherichia coli 0111:b4), for 40 minutes at 37 degrees C before the adherence and cytotoxicity assays. Human umbilical vein endothelial monolayers were stimulated with tumor necrosis factor alpha, 25 ng/mL, and interleukin 1 beta, 15 U/mL, for 3 hours. The PMNs or EC cells were labeled with sodium chromate Cr 51 and used in a standard adherence or killing assay as required. RESULTS: Control and preoperative patient PMN treatment with lipopolysaccharide produced a modest increase in adherence. The PMNs from patients with systemic inflammatory response syndrome showed moderately increased human umbilical vein endothelial cell adherence, and this could not be augmented further with lipopolysaccharide stimulation. There was a marked increase in PMN adherence to EC after EC activation in all study groups (P < .001). Similar to the adherence data, human umbilical vein endothelial cell cytotoxicity was significantly increased in all groups after human umbilical vein endothelial cell activation (P < .01) but not after PMN stimulation with lipopolysaccharide. CONCLUSION: These data suggest that stimulation of ECs is far more important in producing increased adherence and cytotoxicity of EC than PMN stimulation with lipopolysaccharide in all study groups. Therapeutic efforts in patients with systemic inflammatory response syndrome should be focused on the EC.     

Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R. METHODS: Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored. RESULTS: Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion. CONCLUSIONS: IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.     

Systemic inflammatory response syndrome

BACKGROUND: Localized inflammation is a physiological protective response which is generally tightly controlled by the body at the site of injury. Loss of this local control or an overly activated response results in an exaggerated systemic response which is clinically identified as systemic inflammatory response syndrome (SIRS). Compensatory mechanisms are initiated in concert with SIRS and outcome (resolution, multiple organ dysfunction syndrome or death) is dependent on the balance of SIRS and such compensatory mechanisms. No directed therapies have been successful to date in influencing outcome. METHOD: This review examines the current spectrum and pathophysiology of SIRS. RESULTS AND CONCLUSION: Further clinical and basic scientific research is required to develop the global picture of SIRS, its associated family of syndromes and their natural histories.     

The relationship of packed cell transfusion to red blood cell deformability in systemic inflammatory response syndrome patients

Minor traumatic brain injury accounts for the majority of the one million head trauma attendances at A&E departments in the United Kingdom. Guidelines have been established listing criteria for skull films, admission to hospital, computed tomography, and neurosurgical consultation. These are currently undergoing revision and were the subject of a satellite symposium to the J Douglas Miller memorial meeting held in October 1996 in Edinburgh. In the East Anglia Region the current guidelines have been issued as memo-cards for A&E officers. The aim of admission is to observe for deterioration, predominantly caused by intracranial haematomas. The indicators for the development of such lesions are an impaired level of consciousness and presence of a skull fracture. Such patients should therefore undergo regular and frequent neurological observations, and be admitted for at least 12 hours. Following discharge, routine follow up should be considered to identify and treat patients with postconcussion symptoms and signs. The possible way forward for the management of these patients is adopting a greater emphasis on preventative aspects, and establishing, implementing, and auditing evidence based guidelines. Improved teaching in the form of formal induction seminars and computerised teaching aids is required, and a better understanding of the aetiology and treatment of the postconcussion syndrome.     

The fetal inflammatory response syndrome

A mathematical model of the ARDS lung, with simulated gravitational superimposed pressure, evaluated the effect of varying alveolar threshold opening pressures (TOP), PEEP and peak inspiratory pressure (PIP) on the static pressure-volume (PV) curve. The lower inflection point (Pflex) was affected by SP and TOP, and did not accurately indicate PEEP required to prevent end-expiratory collapse. Reinflation of collapsed lung units (recruitment) continued on the linear portion of the PV curve, which had a slope at any volume greater than the total compliance of aerated alveoli. As recruitment diminished, the reduced PV slope could produce an upper Pflex at 20 to 30 cm H2O pressure. An upper Pflex caused by alveolar overdistension could be modified or eliminated by recruitment with high TOP. With constant PIP as PEEP increased, and TOP range of 5 to 60 cm H2O, PEEP to prevent end-expiratory collapse was indicated by minimum PV slope above 20 cm H2O, minimum hysteresis, and maximum volume at a pressure of 20 cm H2O. With constant inflation volume as PEEP increased, the effect on PV slope was unpredictable. Although increased PV slope indicated recruitment, maximum PV slope usually underestimated PEEP required to prevent end-expiratory collapse. Therefore, with this model the PV curve did not reliably predict optimal ventilator settings.     

Antioxidants and inflammatory cell response in preeclampsia

We have previously reported that gastrin induces a rapid and transient tyrosine phosphorylation of phospholipase C gamma 1 (PLC gamma 1) in association with inositol 1,4,5-trisphosphate (IP3) formation in rat colonic epithelial cells (34). In this study, we demonstrate that gastrin regulates IP3 formation mainly through PLC gamma 1 isozyme. Immunoblotting analysis revealed the expression of PLC beta 3 and -gamma 1, but not PLC beta 1, -beta 2, or -beta 4 in the rat colonic epitheliums. To explore what PLC isozyme(s) modulates gastrin effect on IP3, immunoneutralizing antibody to PLC beta 1, -beta 3, or -gamma 1 was introduced into the colonic cells using a lipid carrier. The gastrin-stimulated increase in IP3 concentration was specifically prevented by anti-PLC gamma 1 but not by anti-PLC beta 1 or -beta 3 antibody. Immunoprecipitation assays have also revealed that gastrin promoted an increase in tyrosine phosphorylation and co-precipitation of a 60 kDa src kinase with PLC gamma 1. Administration of antibody specific to pp60c-src into the colonic cells prevented the gastrin-stimulated increases in IP3. Tyrosine phosphorylation of PLC gamma 1 may be a major mechanism through which gastrin regulates IP3 level in the colonic cells. Pretreatment of cells with the tyrosine kinase inhibitor genistein abrogated gastrin's effect on IP3, while extended pretreatment with pertussis toxin, a G-protein inhibitor, did not affect the ability of gastrin to stimulate IP3 formation. Colonic cells expressed the G alpha i subunits1-3; however, immunoblotting analysis did not reveal any difference in G alpha i proteins' expression between control and gastrin treated cells. The results provide direct evidence that gastrin regulates IP3 level by a signaling mechanism that involves PLC gamma 1 and pp60c-src kinase.     

Laparoscopic surgery and the systemic immune response

New York Online Access to Health (NOAH) is a Web site that provides accurate, timely, relevant, and unbiased full-text health information in both English and Spanish. A joint project of The City University of New York Office of Library Services, The New York Academy of Medicine Library, the Metropolitan New York Library Council, and The New York Public Library, NOAH brings consumer health information to the public in New York City and around the world via the Internet. NOAH is an example of a successful collaboration among different types of libraries (academic, public, medical society) and voluntary health agencies to use new technologies to reach a very broad public. This paper discusses the involvement of the library partners in terms of the management and funding of the site. Web site construction is described including how the information is gathered and organized. Future plans and funding issues for NOAH are considered in terms of the expected increase in the need for consumer health information. NOAH can be reached at: www.noah.cuny.edu.     

Disseminated intravascular coagulation and sustained systemic inflammatory response syndrome predict organ dysfunctions after trauma: application of clinical decision analysis

OBJECTIVE: To compare the construct validity and sensitivity to change of 2 spondylitis-specific measures of functional disability, the Health Assessment Questionnaire Disability Index modified for the spondyloarthropathies (HAQ-S) and the Dougados Functional Index, with 2 more generic instruments, the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales-2 (AIMS2), in patients with ankylosing spondylitis (AS). METHODS: Construct validity was assessed in 2 ways: (1) by comparisons of the cross sectional correlations between each functional disability instrument and 6 measures of physical impairment in 216 patients, and (2) by relating changes over time in the HAQ-S and the Functional Index with changes in patient reported pain and stiffness in 153 patients followed for at least 2 years. Sensitivity to change was measured from the responses of 155 patients who reported a qualitative change in the activity of their AS during followup. RESULTS: Most patients had mild functional disability, with median scores of 0.5 on the HAQ-S (possible range 0-3), 0.375 on the HAQ (possible range 0-3), 11 on the Functional Index (possible range 0-40), and 5 on the AIMS2 (possible range 0-60). Scores on the HAQ-S (R2 = 0.24) and the unmodified HAQ (R2 = 0.18) were more highly correlated with measures of physical impairment than were scores on the AIMS2 (R2 = 0.10) or the Functional Index (R2 = 0.09). Changes over time in the HAQ-S and HAQ were more closely related to changes in pain and stiffness than were changes in the Functional Index. The HAQ-S and HAQ were also more sensitive to change than the Functional Index. CONCLUSION: The HAQ-S showed greater construct validity and sensitivity to change than the Functional Index, but performed similarly to the unmodified HAQ.     

Sports in patients with systemic inflammatory musculoskeletal diseases

A 73-year old woman consulted our hospital for consciousness disorder and was hospitalized under a diagnosis of cerebral infarction. On admission, retention of a large volume of ascites was noted. There were also marked increases in tumor markers. Serum CEA, CA19-9 and CA125 levels were 871.9 ng/ml, 1048.2U/ml, and 444.7U/ml, respectively. Cytological examination of the ascites showed class V. Abdominal CT showed a mass measuring 4 cm in diameter and dilatation of the small intestinal tract. During detailed examination, she developed ileus. Fluoroscopy through the lung tube suggested a small intestinal tumor. Laparotomy was performed to relieve ileus. In the abdominal cavity, the greater omentum formed a mass due to dissemination. Tumor was found in the jejunum approximately 60 cm from Treitz's ligament toward the anal side. Omentectomy and partial jejunectomy were performed. Macroscopic findings showed tumor protruding from the mucosal surface. Histological diagnosis was mucinous adenocarcinoma. Primary small intestinal cancer is very rare. In particular, only one case of mucinous adenocarcinoma of the small intestine was reported in Japan. We reported the second case in Japan with a review of the literature.     

Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome

OBJECTIVE: To compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure. DESIGN: Randomized crossover, clinical study. SETTING: University teaching hospital. PATIENTS: Thirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy. INTERVENTION: Patients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9+/-0.8 (SD) mL/min for CVVHD and 3.3+/-1.5 mL/min for CVVH, (p< .01). Plasma endotoxin concentrations were not different between therapies. CONCLUSION: CVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations.     

Persistent inflammatory response in stroke survivors

OBJECTIVE: Goals were to determine how long acute-phase markers remain elevated after ischemic stroke and how marker levels relate to stroke risk factors, stroke mechanism, and subsequent vascular events. METHODS: Fibrinogen (FIB), C-reactive protein (CRP), leukocytes (WBC), neutrophils (PMN), interleukin-6, and interleukin-1 receptor antagonist were measured at stroke onset and at 6 weeks, 6 months, and 1 year after enrollment, or until a vascular event occurred in 136 acute ischemic stroke patients, 76 patients with comparable risk factors for stroke, and 48 age-balanced healthy subjects. RESULTS: Multivariate logistic analysis showed that prior stroke and FIB level predicted new events in stroke patients (p < 0.04 for both), whereas congestive heart failure (p < 0.02) and creatinine level (p < 0.006) were predictive in at-risk patients. After controlling for infection, FIB, CRP, and PMN levels at baseline were higher in at-risk but not in stroke patients with recurrent events (p < 0.05 for all). At 1 year, FIB levels remained elevated in event-free stroke survivors compared with levels in the risk and control groups (p < 0.001 for both). FIB also remained higher in stroke survivors who had atheroembolism (AE) compared with non-AE stroke survivors (381+/-72 versus 342+/-78 mg/dL, p < 0.02). Peripheral vascular disease was an independent predictor (p < 0.0001) of longitudinal FIB in stroke survivors. Of note, both WBC and PMN levels were chronically elevated in patients with stroke risk factors and in stroke survivors (p < 0.0001 for both) compared with healthy elderly subjects. CONCLUSIONS: Most acute-phase markers decline gradually after stroke, but FIB remains significantly elevated and is associated with increased risk for recurrent vascular events.     

The nonspecific inflammatory response to injury

PURPOSE: The role of the nonspecific inflammatory response in causing injury related to surgery has become better understood over the last decade. There are complex interactions between neutrophils, cytokines and nitric oxide metabolites that may cause organ injury following surgery. The purpose of this review is to summarize some of the processes causing injury through these nonspecific pathways. METHODS: A review of the medical and anaesthetic literature related to inflammation, neutrophils and pro-inflammatory cytokines were performed using Medline. Bibliographies of relevant articles were searched and additional articles were then selected and reviewed. RESULTS: Pro-inflammatory cytokines, such as tumour necrosis factor, are released in response to a variety of noxious stimuli (e.g. burns, sepsis, or CABG surgery). These cytokines cause activation of neutrophils with increased upregulation of adhesion complexes on neutrophils and vascular endothelium. Nitric oxide synthase activity is also increased with a resultant increased production of nitric oxide. The increased nitric oxide concentration in the presence of superoxide free radicals secreted by activated neutrophils forms peroxynitrite, a more reactive and toxic molecule. Once this process is initiated, diffuse organ injury can result. Although some information related to specific anaesthetics is available, firm recommendations related to clinical practice cannot be made. CONCLUSIONS: There is a complex interplay of inflammatory mediators that can cause injury. Although specific clinical applications for manipulating these pathways are not yet generally available, this area holds promise to develop new techniques to improve outcomes following surgery.     

Postoperative inflammatory response after autologous and allogeneic blood transfusion

BACKGROUND: Allogeneic blood transfusions cause immunosuppression. The aim of this study was to determine whether complement anaphylatoxins, cytokines, or both are released in the recipient, after blood transfusions in general, and after autologous blood transfusions in particular. METHODS: Thirty-one patients having total hip joint replacement surgery were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). Plasma concentrations of the anaphylatoxins C3a and C5a, the terminal C5b-9 complement complex, and cytokines IL-6 and IL-8 in the recipients were repeatedly analyzed before, during, and after surgery. RESULTS: Significantly increased concentrations of IL-6 and IL-8 appeared in both groups, with a significantly greater increase in the autologous blood group. Patients in both groups developed a moderate but significant increase of C3a without a significant difference between them. C5a and terminal C5b-9 complement complex were not greatly changed. CONCLUSIONS: The study showed a greater increase in cytokine concentration after autologous blood transfusion than after allogeneic blood transfusion. The lower response in the latter may result from transfusion-induced suppression of cellular immunity.     

Release of mediators of systemic inflammatory response syndrome in the course of a severe delayed hemolytic transfusion reaction caused by anti-D

Cells from primary porcine hepatocytes (PPH) and the immortalized human hepatoma cell line C3A are both used in bioartificial liver support systems (BALSS). In this work the viability and metabolic capacity of PPH and C3A cells cultured in different media were compared. Also, because the cells come into direct or indirect contact with human blood components in BALSS, the effects of human complement on survival and functions of the cells was evaluated. For short-term culture, maintenance of PPH viability was essential for retention of P450IA1 activity (r = 0.882, p < 0.01) and effective ammonia clearance (r = -0.791, p < 0.01). When cell viability was below 60% P450IA1 activity could not be recorded and nitrogen elimination activity significantly diminished. In contrast to PPH, ammonia levels were markedly increased for C3A cells in all culture media tested (p < 0.01). Ammonia increase correlated with C3A viability (r = 0.896, p < 0.05). PPH metabolic function was superior to that of the C3A cell line when evaluated by P450IA1 activity, ammonia removal, and amino acid metabolism. When PPH were incubated in human plasma (HP) or human serum (HS) there was rapid and irreversible deterioration of viability occurring within 9 h. This toxic effect could be prevented by the inactivation of complement. When sodium citrate dissolved in dextrose was added to medium, there was considerable damage to both PPH and the C3A cell line. However, there was no demonstrable toxic effect when hepatic cells of either type were exposed to heparin. We conclude that PPH cultivated in complement-inactivated HP or HS are to be preferred to C3A for clinical application of BALSS, and that heparin should be preferred for anticoagulation in BALSS.