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 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.     

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 alcohol syndrome: symptoms and pathogenesis

The symptoms of the fetal alcohol syndrome and their frequency of appearance are described based on 41 reports in the literature and on own observations. Experimental evidence is presented proving the lack of cytotoxicity, mutagenicity and teratogenicity of alcohol itself and the intensive cytotoxicity, mutagenicity and teratogenicity of acetaldehyde. Responsibility for the fetal alcohol syndrome is ascribed to acetaldehyde at maternal blood concentrations surpassing 35 micrometer and it is suggested that the raised acetaldehyde level is due to an inherited or acquired defect of mitochondrial aldehyde dehydrogenase. Prospective mothers displaying acetaldehyde levels exceeding 30 micrometer after a drink should be advised against bearing a child.     

The response of the fetal heart rate of amniocentesis

Fetal heart rate monitoring during 107 amniocenteses suggested that acceleration of the fetal heart rate indicated fetal well-being. Eight out of the 19 fetuses who did not show this response (as against 2 out of the 88 others) had a low Apgar score at birth.     

Septicemia and systemic inflammatory response

To determine the relation between endocarditis/septicemia and systemic inflammatory response syndrome (SIRS), septic shock, MODS, we performed a retrospective analysis in 196 HIV-negative patients, with endocarditis/septicemia. No deaths were observed between 20 patients with endocarditis without severe infective SIRS/septic shock. On the other hand among 10 patients with endocarditis with severe infective SIRS/septic shock we registered 3 deaths (P = 0.052). No deaths were registered among 93 patients with septicemia without severe infective SIRS/septic shock. Between 73 patients with septicemia and severe infective SIRS/septic shock 9 (12.3%) patients died and, precisely, 7/61 in severe infective SIRS (11.4%) and 2/.12 (16.6%) in septic shock (P = 0.003). The definition of septicemia according to Schottmüller (1914), as a generalized bacterial infection with a persistent bacteremia is still justified. The term "sepsis" has become ambiguous because it has been used as synonym of "acute response to infection", while in the past and presently, at least in Europe, it is synonym of septicemia, persistent bacteremia. The term of SIRS could avoid the misunderstanding. The words: "infective SIRS", "severe infective SIRS", may label properly the reactive events mounted by the host as a useful defence against infections but they become dangerous and bring about septic shock, organ failure and mortality when excessive.     

Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: the BioLogic-Detoxification Plasma Filtration System

Systemic inflammatory response syndrome (SIRS) is one of the most common causes of death in intensive care unit patients. The detoxification plasma filtration (DTPF) system (HemoCleanse, Inc., West Lafayette, IN) combines the DT hemodiabsorption system in series with a push-pull pheresis PF system (a suspension of powdered sorbents surrounding 0.5 microm plasma filter membranes). Bidirectional plasma flow (at 80-100 ml/min) across the PF membranes provides direct contact between plasma proteins and powdered sorbents, as well as clearance of cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) at a rate of 15-25 ml/min, without evidence of saturation for 90 minutes. In a U.S. Food and Drug Administration approved study we treated eight patients with SIRS and organ failure with a single DTPF treatment, using powdered charcoal as sorbent in four patients and powdered charcoal and silica in four patients. Treatments proceeded for 6 hours with proper heparin anticoagulation (activated clotting time 250-300 sec) and appeared safe. All patients improved during the treatments and each had increased blood pressure and decreased need for pressor agents. Plasma cytokine levels stabilized or decreased during treatment and were significantly lower the morning after treatment. Multiple organ dysfunction (MOD) and Acute Physiology Chronic Health Evaluation II scores and organ function gradually improved in most patients, and two patients survived for more than 28 days and two for more than 14 days. The DTPF System may prove beneficial in treatment of patients with sepsis.     

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.     

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.     

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.     

Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects

PURPOSE: To investigate the aerobic and anaerobic microbiology of dacryocystitis. METHOD: Retrospective review of the 62 clinical and microbiologic records collected between 1980 and 1990. RESULTS: Aerobic or facultative bacteria were recovered in 32 cases (52%), anaerobic bacteria only in 20 cases (32%), mixed aerobic and anaerobic bacteria in seven cases (11%), and fungi in three cases (5%). A total of 94 organisms (1.5 per specimen), which included 56 aerobic or facultative anaerobic organisms, 35 anaerobic organisms, and three fungi, were recovered. The predominant aerobic and facultative bacteria were Staphylococcus aureus (15 isolates), Staphylococcus epidermidis (13 isolates), and Pseudomonas species (seven isolates). The most frequently recovered anaerobes were Peptostreptococcus species (13 isolates), Propionibacterium species (12 isolates), Prevotella species (four isolates), and Fusobacterium species (three isolates). The predominant fungus was Candida albicans (two isolates). Polymicrobial infection was present in 28 cases (45%). CONCLUSION: These data highlight the potential importance of anaerobic bacteria in dacryocystitis.     

The inflammatory and immune response to mousepox (infectious ectromelia) virus

The ectromelia virus (EV) has been recognized as the etiological agent of a relatively common infection in laboratory mouse colonies around the world, i.e., Europe (including Poland), USA and Asia. Due to widespread use of mice in biomedical research, it is important to study the biology of strains characteristic for a given country. This is particularly significant for the diagnosis, prevention and control ectromelia. In severe epizootics, approximately 90% morbidity is observed within colonies and mortality rate exceeding 70% is observed within 4 to 20 days from the appearance of clinical symptoms. The resistance to lethal infection is mouse strain-dependent. Several inbred strains of mice, including C57BL/6 and AKR are resistant to the lethal effects of EV infection, while others, such as A and BALB/c are susceptible. Recent studies indicate that (1) T lymphocytes, NK cells and interferon (IFN)-dependent host defenses must operate for the expression of resistance, (2) virus-specific T-cell precursors appear earlier in regional lymph nodes of resistant than susceptible mice, and (3) resistance mechanisms are expressed during early stages of infection. Over the past several years, (1) induction of anti-EV cytotoxic CD8+ T lymphocytes (CTL) responses in vivo in the absence of CD4+ (T helper) cells, (2) importance of some cytokines e.g., IFN-gamma in EV clearance at all stages of infection, and (3) induction of nitric oxide (NO) synthase, which is necessary for a substantial antiviral activity of IFN-gamma, have been demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

A male with fetal valproate syndrome and autism

Fetal valproate syndrome (FVS) is characterized by minor craniofacial anomalies, major organ malformations, and developmental delay. We report on a patient who has a clinical phenotype compatible with both FVS and autism. The presence of an autistic disorder in a previously reported case of FVS and similar findings in our patient suggest that a relation between this known teratogen and autism may exist.     

Bone age and growth in fetal alcohol syndrome

We have found delayed mean bone age in 63 children with fetal alcohol syndrome (FAS). The mean bone age Z-score for boys (n = 31) was -2.12 SDs and for girls (n = 32) was -1.62 SDs. This might suggest that they have potential for catch-up growth. However, experience with children with intrauterine growth retardation suggests that this will not be the case and that FAS children will be of reduced height at maturity. Further support for this assumption was gained from a sample of 26 patients who were followed until at least the age of 14 years for females and 16 years for males. There was no significant change in height Z-scores from early childhood to early adulthood, the mean score being -2.16 SDs and -2.11 SDs at mean ages of 4.83 years and 18.69 years, respectively. On the other hand, there were significant changes in weight and head circumference. The mean weight Z-score changed from -2.10 SDs to -1.14 SDs (p < 0.001). The head circumference mean Z-score in 16 patients was -3.13 SDs at a mean age of 2.79 years and -2.63 SDs at a mean age of 17.37 years (p = 0.013). Short stature can continue to be used as a diagnostic criterion for FAS beyond childhood.     

Chronic intestinal pseudoobstruction associated with fetal alcohol syndrome

Alcohol acts as a teratogen in the fetus, resulting in prenatal or postnatal growth failure, characteristic facial dysmorphic features, and central nervous system dysfunction. The toxic effects of alcohol on the developing brain are well recognized, but gastrointestinal neuropathy has not been described in fetal alcohol syndrome (FAS). Five children with FAS presented in infancy with signs and symptoms suggestive of chronic intestinal pseudoobstruction. They were not able to sustain adequate caloric intake by mouth, and all required prolonged special methods of alimentation. We performed antroduodenal manometry in these children to determine whether their symptoms were associated with a gastrointestinal motility disorder. All patients had abnormally propagating phase III-like episodes during fasting (retrograde in four, simultaneous in two). Persistent clusters of stationary contractions were a prominent feature in two patients. In utero neurotoxicity of alcohol may not be limited to the central nervous system, but may also cause an enteric neuropathy presenting in infancy as chronic intestinal pseudoobstruction.     

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.