Missed myocardial infarctions in ED patients prospectively categorized as low risk by established risk scores.

STUDY OBJECTIVES: Few studies have prospectively compared multiple cardiac risk prediction scores. We compared the rate of missed acute myocardial infarction (AMI) in chest pain patients prospectively categorized as low risk by unstructured clinical impression, and by HEART, TIMI, GRACE, and EDACS scores, in combination with two negative contemporary cardiac troponins (cTn) available in the U.S. METHODS: We enrolled 434 patients with chest pain presenting to one of seven emergency departments (ED). Risk scores were prospectively calculated and included the first two cTn. Low risk was defined for each score as HEART≤3, TIMI≤0, GRACE≤50, and EDACS≤15. AMI incidence was calculated for low risk patients and compared across scores using Χ2 tests and C statistics. RESULTS: The patients' median age was 57, 58% were male, 60% white, and 80 (18%) had AMI. The missed AMI rate in low risk patients for each of the scores when combined with 2 cTn were HEART 3.6%, TIMI 0%, GRACE 6.3%, EDACS 0.9%, and unstructured clinical impression 0%. The C-statistic was greatest for the EDACS score, 0.94 (95% CI, 0.92-0.97). CONCLUSIONS: Using their recommended cutpoints and non high sensitivity cTn, TIMI and unstructured clinical impression were the only scores with no missed cases of AMI. Using lower cutpoints (GRACE≤48, TIMI=0, EDACS≤11, HEART≤2) missed no case of AMI, but classified less patients as low-risk.

Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism.

End tidal carbon dioxide tension (P(ET,CO(2))) is a surrogate for dead space ventilation which may be useful in the evaluation of pulmonary embolism (PE). We aimed to define the optimal P(ET,CO(2)) level to exclude PE in patients evaluated for possible thromboembolism. 298 patients were enrolled over 6 months at a single academic centre. P(ET,CO(2)) was measured within 24 h of contrast-enhanced helical computed tomography, lower extremity duplex or ventilation/perfusion scan. Performance characteristics were measured by comparing test results with clinical diagnosis of PE. PE was diagnosed in 39 (13%) patients. Mean P( ET,CO(2)) in healthy volunteers did not differ from P( ET,CO(2)) in patients without PE (36.3+/-2.8 versus 35.5+/-6.8 mmHg). P(ET,CO(2 )) in patients with PE was 30.5+/-5.5 mmHg (p<0.001 versus patients without PE). A P(ET,CO(2)) of >or=36 mmHg had optimal sensitivity and specificity (87.2 and 53.0%, respectively) with a negative predictive value of 96.6% (95% CI 92.3-98.5). This increased to 97.6% (95% CI 93.2-99.) when combined with Wells score <4. A P(ET,CO(2)) of >or=36 mmHg may reliably exclude PE. Accuracy is augmented by combination with Wells score. P( ET,CO(2)) should be prospectively compared to D-dimer in accuracy and simplicity to exclude PE.

Management of penetrating neck injury in the emergency department: a structured literature review.

OBJECTIVE: The management of patients with penetrating neck injuries in the prehospital setting and in the emergency department has evolved with regard to the necessity for spinal immobilisation and the use of multidetector computed tomographic (MDCT) imaging. Questions also arise as to choices of securing a threatened or compromised airway. A structured review of the medical literature was conducted to provide current recommendations for the management of patients with penetrating neck injury. METHODS: Databases for PubMed, MEDLINE, CINAHL and Cochrane EBM Reviews were electronically searched using the subject headings "penetrating neck injury", "penetrating neck trauma", "cervical immobilization", "multi-detector CTA" and "airway management". The results generated by the search were limited to English language articles and reviewed for relevance to the topic. RESULTS: 122 citations were identified that met the criteria for emphasis on emergency department care, cervical spine immobilisation, use of multidetector CT angiography or airway management. After excluding case series, non-peer reviewed articles and editorials, 20 articles were identified and reviewed. CONCLUSIONS: The current literature suggests that prehospital cervical immobilisation may not be necessary unless the patient has focal neurological deficits. Studies show that patients with penetrating neck trauma who are haemodynamically stable and exhibit no "hard signs" of vascular injury may be evaluated initially by MDCT imaging even when platysma violation is present. Airway management is evolving, but traditional laryngoscopy continues to be the mainstay of airway stabilisation.

Self-reported cardiac risk factors in emergency department nurses and paramedics.

STUDY OBJECTIVE: Our objective was to assess the prevalence of cardiac risk factors in a sample of urban paramedics and emergency department (ED) nurses. METHODS: We asked 175 paramedics and ED nurses working at a busy, urban ED to complete a cardiovascular risk assessment. The survey asked subjects to report smoking history, diet, exercise habits, weight, stress levels, medication use, history of hypertension or cardiac disease, family history of cardiovascular disease (CVD), and cholesterol level (if known). RESULTS: 129 of 175 surveys were returned (74% return rate) by 85 paramedics and 44 nurses. The percentages of paramedics and nurses at high or very high risk for cardiac disease were 48% and 41%, respectively. Forty-one percent of female respondents and 46% of male respondents were at high or very high risk. Cigarette smoking was reported in 19% of the paramedics and 14% of the nurses. The percentages of paramedics and nurses who reported hypertension were 13% and 11%, respectively. High cholesterol was reported in 31% of paramedics and 16% of nurses. CONCLUSIONS: Forty-eight percent of paramedics and 41% of ED nurses at this center are at high or very high risk for cardiovascular disease, by self-report. Efforts should be made to better educate and intervene in this population of health-care providers in order to reduce their cardiac risk.

Removal of cytokine inducing substances by polymyxin-B immobilized polystyrene-derivative fibers during in vitro hemoperfusion of 10% human plasma containing Staphylococcus aureus challenge.

Staphylococcus aureus (S. aureus) is frequently isolated from blood cultures in the hospital setting. The pathogenesis of S. aureus bacteremia probably replicates mechanisms implicated in gram negative bacterial infections. Cell wall components, such as peptidoglycans and lipoteichoic acids (LTA), can trigger cytokine production. Polymyxin-B (PMX-B) is a cationic peptide that binds endotoxin (ET) and inhibits its activity. Based on this principle, PMX-B was incorporated in polystyrene-derivative fibers, creating a hemoperfusion column (PMX-20R) that removes ET. The authors assessed whether S. aureus possesses PMX-B suppressible cytokine-inducing substances, and whether LTA, an anionic molecule, is one such substance. Heparinized blood was obtained from healthy volunteers, peripheral blood mononuclear cells (PBMC) were isolated by Ficoll-Hypaque separation, and 10% human plasma prepared. PBMC were incubated with 1, 5, or 10 microg/ml of S. aureus LTA, with and without 10 microg/ml of PMX-B. Also, using PMX-20R, in vitro hemoperfusion (IVH) was performed with 10% human plasma containing a 1:1,000 dilution of S. aureus challenge at 100 ml/min for 2 hours at 37 degrees C, and plasma obtained before and after IVH was incubated with PBMC. After a 24 hour incubation at 37 degrees C, PBMC were subjected to three freeze-thaw cycles, and total TNFalpha was measured by radioimmunoassay. TNFalpha production by PBMC incubated with LTA was 164+/-4 pg, 324+/-54 pg, 657+/-55 pg, and 1143+/-215 pg in control, and LTA 1, 5, and 10 microg/ml, respectively. The addition of PMX-B resulted in a 40+/-12% (p = 0.02), 61+/-6% (p = 0.002), and 62+/-14% (p = 0.02) decrease in TNFalpha production, respectively. Before IVH, TNFalpha production by PBMC incubated with 10% plasma containing S. aureus challenge was 1275+/-70 pg. After 2 hours of IVH, the decrease in TNFalpha production was 20+/-4% (p = 0.002). In conclusion, S. aureus LTA induces TNFalpha production that is significantly suppressed by PMX-B. Consequently, S. aureus cytokine-inducing substances are removed during IVH with PMX-20R, and this may be due to stoichiometric binding of LTA to PMX-B.

Endotoxin removal by polymyxin-B immobilized polystyrene-derivative fibers during in vitro hemoperfusion of 10% human plasma.

During gram-negative bacterial sepsis, lipid A, the biologically active moiety of endotoxin (ET), activates monocytes and induces the release of cytokines. PMX-B, a cationic peptide, binds to lipid A and inhibits its activity. Based on this principle, PMX-B was incorporated in polystyrene-derivative fibers, creating a hemoperfusion column (PMX-20R) that removes ET. After in vitro characterization of the cytokine inducing potency of three gram-negative bacterial challenges, the authors evaluated the in vitro efficacy of PMX-20R in a model using 10% human plasma. Cytokine production by peripheral blood mononuclear cells (PBMC) incubated with plasma before and after in vitro hemoperfusion (IVH) was used as the index of ET removal. One hundred forty milliliters of heparinized blood were obtained from healthy volunteers. Forty milliliters were used to harvest PBMC at baseline, and 10% plasma prepared from the rest, was challenged with: 1) 0.01, 1, or 100 ng/ml of purified Escherichia coli ET; or 2) 1:1,000 dilution of E. coli, Pseudomonas aeruginosa, or Klebsiella pneumoniae. IVH was performed at 100 ml/min at 37 degrees C for up to 6 hours. One half milliliter samples, drawn before and at designated time intervals after the start of IVH, were mixed with a 0.5 ml suspension of 5 x 10(6) PBMC/ml from the same donor, and incubated for 24 hours at 37 degrees C. PBMC were subjected to three freeze-thaw cycles, and total tumor necrosis factor alpha (TNFalpha) was measured by radioimmunoassay. Before IVH, TNFalpha production by PBMC incubated with 10% plasma containing 0.01, 1, or 100 ng/ml of purified E. coli ET was 1905+/-391 pg, 2076+/-552 pg, and 5304+/-1001 pg, respectively. After 2 hours of IVH, the respective decrease in TNFalpha production was 82+/-5% (p = 0.005), 78+/-10% (p = 0.01), and 95+/-1% (p = 0.002). Before IVH, TNFalpha production by PBMC incubated with 10% plasma containing 1:1,000 dilution of E. coli, P. aeruginosa or K. pneumoniae was 2896+/-273 pg, 1816+/-122 pg, and 1131+/-125 pg, respectively. After 2 hours of IVH, the respective decrease in TNFalpha production was 83+/-4% (p < 0.001), 53+/-4% (p < 0.001), and 70+/-5% (p < 0.001). When IVH was extended to 6 hours, the further decrease in TNFalpha production was not statistically significant. These results suggest an impressive in vitro removal of ET by PMX-20R from 10% human plasma containing either purified E. coli ET or E. coli, P. aeruginosa, or K. pneumoniae. Further in vitro studies are required, using whole blood challenged with gram-negative bacteria.

Transfer of cytokine-inducing bacterial products across hemodialyzer membranes in the presence of plasma or whole blood.

Cytokine production by peripheral blood mononuclear cells (PBMC) is a sensitive indicator of cytokine-inducing substances which may cross from contaminated dialysate into the blood compartment. The objective of this study was to compare the transfer of cytokine-inducing substances from dialysate contaminated with a culture filtrate from Pseudomonas aeruginosa across dialyzers with low (hemophan) or intermediate ultrafiltration coefficients (modified cellulose triacetate, CTA), under conditions where either 10% plasma or whole blood was circulated in the blood compartment. Eight paired experiments of in vitro dialysis were carried out at 37 degrees C using a countercurrent recirculating loop dialysis circuit with either a new CTA or hemophan dialyzer. 10% plasma in standard tissue culture medium was circulated through the blood compartment and bicarbonate dialysate was circulated in the dialysate compartment. The dialysate was challenged sequentially by log-fold dilutions (10(2), 10(3) or 10(4)) of a Ps. aeruginosa culture filtrate. Samples were drawn from the blood compartment 5 and 15 minutes after each challenge and incubated with suspensions of PBMC in the absence or presence of polymyxin B, in order to block endotoxin. After 24 h at 37 degrees C, total interleukin-1 alpha (IL-1 alpha) was measured by RIA. Although the dialysate contained potent cytokine-inducing substances, there was no significant IL-1 alpha production by PBMC incubated with the plasma mixture from the blood compartment in the majority of experiments with both dialyzers and with each of the three dilutions of the bacterial challenge. Eight experiments were also performed with CTA dialzyers using heparinized whole blood in the blood compartment. Samples of whole blood and dialysate were drawn at baseline, after one hour of dialysis with uncontaminated dialysate and 15 minutes and three hours after dialysis with dialysate contaminated with Ps. aeruginosa filtrate. There was no significant IL-1 alpha production by PBMC isolated from the whole blood 1 h after dialysis with uncontaminated dialysate, and 15 min and 2 h after adding the Ps. aeruginosa filtrate to the dialysate side. In contrast, production of IL-1 alpha by PBMC from the same donors incubated with samples from the dialysate were 263 +/- 50, 1074 +/- 306, 2333 +/- 774 and 2602 +/- 702 pg/2.5 x 10(6) PBMC, respectively at the same four time points. These data suggest that although the Ps. aeruginosa culture filtrate present in the dialysate was a potent inducer of IL-1 alpha, neither dialyzer permitted transfer of cytokine inducing substances from the dialysate into the blood compartment.

Transmembrane passage of cytokine-inducing bacterial products across new and reprocessed polysulfone dialyzers.

The widespread use of bicarbonate dialysate and reprocessed high-efficiency and "high-flux" dialyzers has raised concerns about the increased risk of reverse-transfer of dialysate contaminants into the blood compartment. To evaluate this concern, the reverse-transfer of bacterial products from contaminated bicarbonate dialysate into the blood compartment was compared during in vitro dialysis with new or reprocessed high-flux polysulfone dialyzers. In vitro dialysis was carried out at 37 degrees C by use of a counter-current recirculating loop dialysis circuit with either new high-flux polysulfone dialyzers or dialyzers reprocessed once or 20 times with formaldehyde (0.75%) and bleach (< 1%) with an automated system. Heparinized whole blood from healthy volunteers was circulated through the blood compartment, and bicarbonate dialysate was circulated in the dialysate compartment. The dialysate was challenged sequentially by 1:1000 and 1:100 dilutions of a sterile Pseudomonas aeruginosa culture supernatant (bacterial challenge). Samples were drawn from the blood and dialysate compartments 1 h after each challenge. Peripheral blood mononuclear cells (PBMC) were harvested by Ficoll-Hypaque separation from whole blood in the blood compartment and a 5 x 10(6) PBMC/mL cell suspension was prepared. Likewise, dialysate samples (0.5 mL) were added to 0.5 mL suspension of 5 x 10(6) PBMC/mL drawn at baseline. All PBMC suspensions were incubated upright in a humidified atmosphere at 37 degrees C with 5% CO2 for 24 h, and total interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha) cytokine production (cell-associated and secreted) was measured by radioimmunoassay. Eight experiments were performed for each arm of the study with the same donor for each arm. One hour after contaminating the dialysate with a 1:1000 dilution of the bacterial challenge, IL-1 alpha production by PBMC harvested from the blood compartment was 160 +/- 0, 171 +/- 11, and 270 +/- 35 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.004). One hour after challenging the dialysate with 1:100 dilution, IL-1 alpha production by PBMC harvested from the blood compartment was 188 +/- 20, 228 +/- 35, and 427 +/- 67 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.006). IL-1 alpha production by PBMC from dialyzers reprocessed 20 times was significantly greater than both new and dialyzers reprocessed once. However, there were no significant differences between new dialyzers and dialyzers reprocessed once. Similarly, after the 1:1000 challenge, TNF alpha production by PBMC harvested from the blood compartment was 160 +/- 0, 160 +/- 0, and 213 +/- 22 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.008). After the 1:100 challenge, TNF alpha production was 168 +/- 8, 188 +/- 20, and 225 +/- 32 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.20). These results demonstrate that reprocessing of high-flux polysulfone dialyzers with bleach increases the risk of reverse-transfer of bacterial products from contaminated dialysate, and this risk appears to increase with the number of reuses. Consequently, units that reprocess membranes with bleach and have suboptimal water quality might subject their patients to a higher risk of cytokine-related morbidity.

Initial characterization and autoradiographic localization of a novel sigma/opioid binding site in immune tissues.

High concentrations of novel, haloperidol- and DTG-inaccessible (+)-[3H]-3-PPP binding sites were found in human peripheral blood leukocytes rat spleen and splenocytes, but not in rat brain. Splenic sites were localized in a course punctate pattern in the marginal zones and red pulp. The pharmacology of the splenic sites was: (-)-SKF 10,047 > or = naltrexone = (-)-pentazocine > (+)-pentazocine = (-)-3-PPP = (+)-SKF 10,047 > or = (+)-3-PPP > or = dextrorphan > dextromethorphan > PCP > clorgyline. DTG, haloperidol, TCP, (-)-deprenyl and SKF 525-A did not complete. Binding activity was destroyed by heating and phospholipase C, but not by proteases or glycosidases. These sites may be involved in immunomodulation by opiate and sigma receptor agonists.

Cytokine production by human peripheral blood mononuclear cells stimulated by a Pseudomonas aeruginosa culture filtrate: role of plasma and polymyxin B.

The lack of consensus regarding the significance of transmembrane passage of bacterial products across hemodialysis membranes can be related to several methodological differences in the various studies, including the choice of circulating fluid in the blood compartment of the model, nature and concentration of the bacterial products employed to challenge the dialysate compartment and whether cytokine production by PMBC or the limulus amebocyte lysate (LAL) assay was used as the index of transfer and the cytokine used as the read-out. In this study, we examined the production of interleukin-1 alpha (IL-1 alpha), interleukin-1 receptor antagonist (IL-1Ra) and interleukin-8 (IL-8) by peripheral blood mononuclear cells (PBMC) incubated with a Pseudomonas aeruginosa culture filtrate. Further, the effects of 10% autologous human plasma and Polymyxin B sulfate (PmB) on cytokine production by PBMC were also characterized. The results of our study indicate that the Ps. aeruginosa culture filtrate had both PmB suppressible and PmB non-suppressible components and that the addition of 10% human plasma significantly enhanced cytokine production by both PmB suppressible and PmB non-suppressible components. The enhancing effect of plasma was most evident at low concentrations of the filtrate. The inhibitory effect of PmB was most evident in samples cultured in the presence of 10% plasma. There was a direct correlation between the production of IL-1 alpha and IL-1Ra suggesting that both pro-inflammatory cytokines and cytokine-specific inhibitory proteins are concurrently produced. There results have direct relevance to selection of study conditions for in vitro models used to study the transmembrane passage of bacterial products across hemodialysis membranes.

Suicide bereavement and recovery patterns compared with nonsuicide bereavement patterns.

This study compared bereavement experiences of suicide survivors with those of other survivors. The primary focus of investigation was upon grief reactions suggested to be unique to suicide bereavement and upon quality of grief resolution 2-4 years after death. Fifty-seven women and men, between the ages of 24 and 48, who had experienced the death of a marital partner were interviewed. Subjects were assigned to one of four groups by mode of death (suicide, accident, unanticipated natural, and expected natural). Analyses of variance and Scheffe procedures indicated no significant differences among survivors on frequencies of grief reactions considered common to all bereavements. The suicide survivors were significantly different from all others on certain grief measures, including rejection and unique grief reactions. On various other grief measures, significant differences were indicated among the groups of survivors. Four primary conclusions, implications of the findings, and limitations of the study are discussed.

Development of the Grief Experience Questionnaire.

The development of the Grief Experience Questionnaire (GEQ) is reported. This questionnaire is an instrument for measuring various components of grief, including somatic reactions, general grief reactions, search for explanation, loss of social support, stigmatization, guilt, responsibility, shame, rejection, self-destructive behavior, and reactions to a unique form of death. Initial results with the GEQ suggest its potential to differentiate grief reactions experienced by suicide survivors from those experienced by survivors of accidental death, unexpected natural death, and expected natural death. Conclusions support its use in redressing common methodological criticisms of suicide survivor research. Six additional benefits derived from use of this instrument are discussed.

Energy transfer as parametric excitation: an examination of nonlinearity in enzymatic reaction, nerve conduction, muscle contraction, electron tunneling, and electron transfer.

Chemical parametric excitation is presented as the fundamental mechanism of energy transfer. Together with the Franck-Condon principle, it provides a mechanically sound explanation for enzymatic reaction, nerve excitation, muscle contraction, and electron transfer at a basic level. Intermediate between macroscopic models of membrane asymmetry and molecular models, the new model rests on a systematic approach, proposed here, to organizational aspects of the energy transfer processes. In support, a derivation is given of the chemical analog of the Manley-Rowe power conservation relations for parametrically excited electrical networks. This extension to chemical systems indicates for the first time an explanation of power flow directionality and delegates a pumping role to the enzyme. The generalized Manley-Rowe relations are suggested to be a universal law of nature. In such case, nonlinearity could be attributable to the coupling of three systems by these generalized Manley-Rowe conditions relating flows/reactions/oscillations--even though separately each system might be described by linear (Onsager) relations.