Search

Pathological abdominal adhesions can cause bowel obstructions. A history of appendectomy (appy) increases patient rehospitalization risk directly related to adhesions. To potentially identify strategies for adhesion treatment, we characterized reactive ascites (rA) collected during appy or adhesiolysis for small bowel obstruction (SBO).This is a non-randomized, prospective observational study recruiting patients with non-perforated appendicitis or SBO from three Level 1 trauma centers in the United States. rA were analyzed via liquid chromatography-mass spectrometry (LC-MS) (n = 31), bead-based quantification cytokines and chemokines (n = 32) and soluble receptors (n = 30), and LC-MS metabolomics (n = 18).LC-MS showed that samples contained albumin, apolipoprotein A1, and transthyretin and that metabolites increased in SBO vs appy rA were biomarkers of oxidative stress. Multi-plex analyses showed levels of 17 cytokines/chemokines and 6 soluble receptors were significantly different in appy vs SBO rA. Top increased proteins in appy compared to SBO rA by 20.14-, 11.53-, and 8.18-fold were granulocyte-colony stimulating factor, C-X-C motif chemokine ligand 10, and interleukin-10, respectively.These data further define pro- and anti-inflammatory mediators and metabolites that may drive formation or perpetuate chronic abdominal adhesions. Future research is to further explore whether attenuation of these factors may decrease pathologic adhesion formation.

Introduction Longer prehospital times were associated with increased odds for survival in trauma patients. The purpose of this study was to determine how the COVID-19 pandemic affected emergency medical services (EMS) prehospital times for trauma patients. Methods This retrospective cohort study compared trauma patients transported via EMS to six US level I trauma centers admitted 1/1/19–12/31/19 (2019) and 3/16/20–6/30/20 (COVID-19). Outcomes included: total EMS pre-hospital time (dispatch to hospital arrival), injury to dispatch time, response time (dispatch to scene arrival), on-scene time (scene arrival to scene departure), and transportation time (scene departure to hospital arrival). Fisher's exact, chi-squared, or Kruskal-Wallis tests were used, alpha = 0.05. All times are presented as median (IQR) minutes. Results There were 9400 trauma patients transported by EMS: 79% in 2019 and 21% during the COVID-19 pandemic. Patients were similar in demographics and transportation mode. Emergency room deaths were also similar between 2019 and COVID-19 [0.6% vs. 0.9%, p = 0.13].There were no differences between 2019 and during COVID-19 for total EMS prehospital time [44 (33, 63) vs. 43 (33, 62), p = 0.12], time from injury to dispatch [16 (6, 55) vs. 16 (7, 77), p = 0.41], response time [7 (5, 12) for both groups, p = 0.27], or on-scene time [16 (12−22) vs. 17 (12,22), p = 0.31]. Compared to 2019, transportation time was significantly shorter during COVID-19 [18 (13, 28) vs. 17 (12, 26), p = 0.01]. Conclusion The median transportation time for trauma patients was marginally significantly shorter during COVID-19; otherwise, EMS prehospital times were not significantly affected by the COVID-19 pandemic.

Objective Cerebral venous thrombosis (CVT) is a rare type of stroke whose pathophysiology differs from arterial stroke. CVT is treated with systemic anticoagulant therapy even in the setting of intracerebral hemorrhage. Patients who do not respond adequately may require decompressive surgery. The study objective was to examine the timing of anticoagulation in patients with CVT who require decompressive surgery through systematic literature review and consecutive case series. Methods A review of the literature was performed through PubMed using key word search to identify case series and cohort studies examining timing of anticoagulation following decompressive surgery. Our case series included 4 patients who had decompressive surgery for hemorrhagic CVT between 1 January, 2015 and 31 December, 2016 at our comprehensive stroke center. Results The literature review summarizes 243 patients from 15 studies whose timing of anticoagulation varied. The review suggests anticoagulation can be safely resumed at 48 hours postoperatively based on larger series and as early as 12 hours in smaller series, especially when delivered as a half or prophylactic dose. In our case series, timing of anticoagulation varied slightly but was started or resumed within 38–44 hours postoperatively in 3 patients and was started at the time of decompressive surgery without interruption in 1 patient. No patient had worsening hemorrhage or new hemorrhage while 2 patients rethrombosed. Conclusions Despite the lack of high-quality studies, this systematic review of patients with CVT requiring decompressive surgery indicates that anticoagulation can be safely initiated or resumed around 24–48 hours postoperatively; our series supports the existing literature.

BACKGROUND: There are multiple reports on the effect of time to surgery for geriatric hip fractures; it remains unclear if earlier intervention is associated with improved mortality, hospital length of stay (HLOS), or cost. METHODS: This was a multi-center retrospective cohort study. Patients (≥65y.) admitted (1/14-1/16) to six level 1 trauma centers for isolated hip fractures were included. Patients were dichotomized into early (≤24 h of admission) or delayed surgery (>24 h). The primary outcome was mortality using the CDC National Death Index. Secondary outcomes included HLOS, complications, and hospital cost. RESULTS: There were 1346 patients, 467 (35%) delayed and 879 (65%) early. The early group had more females (70% vs. 61%, p < 0.001) than the delayed group. The delayed group had a median of 2 comorbidities, whereas the early group had 1, p < 0.001. Mortality and complications were not significantly different between groups. After adjustment, the delayed group had no statistically significant increased risk of dying within one year, OR: 1.1 (95% CI:0.8, 1.5), compared to the early group. The average difference in HLOS was 1.1 days longer for the delayed group, when compared to the early group, p-diff

Objective Hip fracture surgery in geriatric patients on anticoagulants may increase the risk for blood loss. Anticoagulation reversal may lower these risks; however, data on blood loss and transfusions are limited. The study purpose was to compare outcomes between hip fracture patients 1) not on anticoagulants 2) whose anticoagulants were reversed, and 3) whose anticoagulants were not reversed. Methods This four-year retrospective cohort study at six Level 1 Trauma Centers enrolled geriatric patients (≥65) with isolated hip fractures. The primary outcome was total hospital blood loss (ml). Secondary outcomes: hospital length of stay (HLOS) and volume of packed red blood cells (pRBC) transfusions (ml). Statistical analyses included: Fisher’s, chi-squared, Kruskal-Wallis, linear mixed-effect and logistic regression. Bonferroni adjusted alpha = 0.025. Results Of the 459 patients, 189 (41%) were not on anticoagulants, 186 (41%) were reversed, and 84 (18%) were not reversed. The LS mean (SE) blood loss was 134 ml (12) for not reversed patients and 159 (17) for reversed patients; no significant difference compared to those not on anticoagulants [138 (12)], p-diff = 0.14 and 0.83, respectively. The LS mean (SE) HLOS was significantly longer for the reversed patients, 7.7 (0.4) days, when compared to those not on anticoagulants, 6.8 (0.4), p = 0.02, and when compared to those not reversed, 6.3 (0.6), p = 0.01. There was no significant difference in pRBC transfusions. Conclusion Not reversing anticoagulants for geriatric hip fractures was not associated with increased volume of blood loss or transfusions when compared to those reversed. Delayed surgery for anticoagulant reversal may be unnecessary and contributing to an increased HLOS.

Background Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions. Methods Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated. Results The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils. Conclusions Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.

Within the first few hours of a traumatic brain injury, the activity of extracellular matrix degradative enzymes increases. As a result, the blood brain barrier becomes disrupted as secondary white matter injury increases. Anoikis, a form of apoptosis, results from cells detaching from the extracellular matrix leading to cell death. This “homelessness” (anoikis) of cells hinders recovery progression, exacerbating brain injury while disrupting synaptic plasticity and other central nervous system functions. Here, we discuss the current knowledge of molecular pathways and proteins involved in both the activation and inhibition of anoikis.

Making and the ”maker movement” have been growing in popularity as a progressive educational approach. However, researchers have leveled critiques of making as being exclusionary toward people with disabilities. In this paper, we present results from the iterative design, implementation and evaluation of Inclusive Making, an undergraduate and graduate level course on accessibility in making. Students in the course went through a ten-week process, culminating in the design of accessibility solutions to include communities with disabilities in making. Using qualitative methods, we chronicle students’ design products, processes and learning in relation to the course iterations. Results show that when students worked with external stakeholders, their designs and learning improved. Moreover, designing for neurodiverse children required students to grapple with existing literature about making in education. We discuss insights from our work regarding the need for more accessibility research in making, and the potential of university students to promote accessible making by engaging with external stakeholders.

It has long been appreciated that the microtubule network plays a critical role in endothelial cell function. Chemical inhibition of tubulin polymerization has been shown to drastically increases endothelial permeability via interactions with the actin cytoskeleton. Conversely, stabilization of microtubules significantly decreases vascular permeability. The purpose of this investigation was to determine if the low molecular weight fraction of commercial 5% human serum albumin (LMWF5A) alters endothelial cell cytoskeletal dynamics and function. To investigate this, human retinal endothelial cells (HREC) were treated with LMWF5A and the acetylation of α-tubulin was determined by immunofluorescent staining and immunoblotting. In addition, permeability assays were performed to evaluate functional changes. We found that HREC treated with LMWF5A exhibit a rapid increase in the amount and distribution of acetylated α-tubulin. This was accompanied by a reduction in macromolecular permeability. Calcium depletion and inhibition of PI3-kinase reduced LMWF5A-induced acetylation while p38 MAPK inhibition potentiated this effect. These findings suggest that LMWF5A mediates changes in the microtubule network and reduces transcytosis in HREC.

Activation of the innate immune system involves a series of events designed to counteract the initial insult followed by the clearance of debris and promotion of healing. Aberrant regulation can lead to systemic inflammatory response syndrome, multiple organ failure, and chronic inflammation. A better understanding of the innate immune response may help manage complications while allowing for proper immune progression. In this study, the ability of several classes of anti-inflammatory drugs to affect LPS-induced cytokine and prostaglandin release from peripheral blood mononuclear cells (PBMC) was evaluated. PBMC were cultured in the presence of dexamethasone (DEX), ibuprofen (IBU), and the low molecular weight fraction of 5% albumin (LMWF5A) followed by stimulation with LPS. After 24 h, TNFα, PGE2, and 15d-PGJ2 release was determined by ELISA. Distinct immunomodulation patterns emerged following LPS stimulation of PBMC in the presence of said compounds. DEX, a steroid with strong immunosuppressive properties, reduced TNFα, PGE2, and 15d-PGJ2 release. IBU caused significant reduction in prostaglandin release while TNFα release was unchanged. An emerging biologic with known anti-inflammatory properties, LMWF5A, significantly reduced TNFα release while enhancing PGE2 and 15d-PGJ2 release. Incubating LMWF5A together with IBU negated this observed increased prostaglandin release without affecting the suppression of TNFα release. Additionally, LMWF5A caused an increase in COX-2 transcription and translation. LMWF5A exhibited a unique immune modulation pattern in PBMC, disparate from steroid or NSAID administration. This enhancement of prostaglandin release (specifically 15d-PGJ2), in conjunction with a decrease in TNFα release, suggests a switch that favors resolution and decreased inflammation.

Background To describe the 4-year experience of symptomatic intracranial hemorrhage (sICH) rate at a high-volume comprehensive stroke center. Methods All admitted adult (≥18 years) patients presenting with an ischemic stroke from 2010 to 2013 were included in this study. The primary outcome was sICH, defined as any hemorrhage with neurological deterioration (change in National Institutes of Health Stroke Scale score ≥4) within 36 hours of intravenous tissue plasminogen activator (IV-tPA) treatment, or any hemorrhage resulting in death. Secondary outcomes were in-hospital mortality and having a favorable modified Rankin Scale (mRS) score (≤2). Results A total of 1925 did not receive intravascular (IV) or intra-arterial (IA) therapy; only 451 received IV therapy; and 175 received both IV and IA therapies. In IV-only patients, the overall rate of sICH was 2.2%; in IV and IA patients, the rate was 5.7%; and in patients who received no therapy, the rate was .4%. The IV-only group had an sICH rate of .9% in 2013. There were no differences in the adjusted odds of dying in the hospital between the study groups. IV-only treatment offered significantly better odds of achieving a favorable functional outcome, compared to no therapy, among patients with moderate stroke severity, whereas IV and IA treatments offered significantly better odds among patients with severe strokes. The odds of achieving a favorable functional outcome by discharge were decreased by 97% if patients suffered an sICH (OR = .03, 95%CI = .004, .19). Conclusions Despite an increased risk of sICH with IV-tPA, treatment with IV-tPA continues to be associated with increased odds of a favorable discharge mRS.

Due to the heterogeneous nature of commercial human serum albumin (cHSA), other components, such as the protease dipeptidyl peptidase IV (DPP-IV), possibly contribute to the therapeutic effect of cHSA. Here, we provide evidence for the first time that DPP-IV activity contributes to the formation of aspartate–alanine diketopiperazine (DA-DKP), a known immunomodulatory molecule from the N terminus of human albumin. cHSA was assayed for DPP-IV activity using a specific DPP-IV substrate and inhibitor. DPP-IV activity was assayed at 37 and 60°C because cHSA solutions are pasteurized at 60°C. DPP-IV activity in cHSA was compared with other sources of albumin such as a recombinant albumin (rHSA). In addition, the production of DA-DKP was measured by negative electrospray ionization/liquid chromatography mass spectrometry (ESI−/LCMS). Significant levels of DPP-IV activity were present in cHSA. This activity was abolished using a specific DPP-IV inhibitor. Fully 70 to 80% DPP-IV activity remained at 60°C compared with the 37°C incubate. No DPP-IV activity was present in rHSA, suggesting that DPP-IV activity is present only in HSA produced using the Cohn fractionation process. The formation of DA-DKP at 60°C was observed with the DPP-IV inhibitor significantly decreasing this formation. DPP-IV activity in cHSA results in the production of DA-DKP, which could account for some of the clinical effects of cHSA.

Background Level I trauma centers have requirements on the percentage of trauma patients admitted to either a trauma surgeon or surgical subspecialist; however, surgical resources are in steady decline. Therefore, a trauma system might better utilize its surgical resources if trained hospitalists admitted a larger percentage of mild to moderately injured trauma patients. The objective of this report is to provide a 5-year evaluation of a trauma medical service (TMED) at treating mild to moderately injured trauma patients. Methods Adult trauma patients consecutively admitted to a Level I trauma center between January 2006 and December 2010 were analyzed. Patients admitted to trauma surgical services were matched 1:1 to those admitted to TMED, via propensity scores. Paired t tests examined differences in hospital duration of stay (DOS), and exact conditional logistic regression examined differences in the odds of having a delayed diagnosis, developing a complication, and dying. Results Of 1,202 TMED patients, 494 were matched; matched TMED patients had similar patient outcomes to nonmatched TMED patients. There were no differences between study groups in the mean hospital DOS, the proportion having a delayed diagnosis, or in the odds of dying in the hospital ( P > .05 for all). The TMED group had a nominally higher complication rate ( P = .12) owing to a higher rate of urinary tract infections. Conclusion Since its inception, the TMED service has successfully and safely treated mild to moderately injured trauma patients, and decreased the dependency on trauma surgical services. Trauma centers might utilize declining surgical services more efficiently with the addition of trauma medical hospitalists.

Breakdown of endothelial barrier function is a hallmark event across a variety of pathologies such as inflammation, cancer, and diabetes. It has also been appreciated that steroid hormones impart direct biological activity on endothelial cells at many levels. The purpose of this investigation was to explore the effect of the androgen-like steroid, danazol, on endothelial cell barrier function in vitro. Primary human endothelial cells exposed to 0.01–50 μM danazol were evaluated for changes in permeability. We found that danazol altered endothelial permeability in a biphasic manner in which nanomolar concentrations enhance barrier function while micromolar concentrations are detrimental. Monitoring of trans-endothelial electrical resistance demonstrated that these barrier enhancing effects were rapid (within 5 min) and lasted for over 24 h. Analysis of intracellular f-actin organization showed that barrier enhancement also correlated with the formation of a submembranous cortical actin ring. Conversely, at higher danazol concentrations, contractile cell phenotypes were observed, represented by stress fiber formation. Competitive binding studies performed using steroid hormone receptor antagonists proved that this activity is the result of androgen and estrogen receptor ligation. These findings suggest that low dose danazol may provide a therapeutic window for diseases involving vascular leakage.

The abbreviated injury scale (AIS) was updated in 2005 from the AIS 1998 version. The purpose of this study is to describe the effects of this change on injury severity scoring and outcome measures.Analyses were performed on all trauma patients consecutively admitted over a 6-month period at two geographically separate Level I trauma centers. Injuries were manually double-coded according to the AIS 05 and the AIS 98. Changes in AIS, ISS, and new ISS (NISS) were analysed using paired t-tests. Apparent differences in outcome by ISS strata (16, 16-24,24) were compared for AIS 05 versus AIS 98 using the Wald-type statistic. Lastly, the percent of patients with a change in ISS strata are reported.There were 2250 patients included in the study. Nearly half (46.4%) of AIS codes changed, resulting in a different AIS score for 18.9% of all codes. The mean ISS was significantly lower using the AIS 05 (11.7) versus the AIS 98 (13.3, p0.001). Similarly, the mean NISS was significantly lower (16.3 versus 18.7, p0.001). In the ISS strata 16-24 an apparent increase in mortality, length of stay, and percent of patients not discharged home was observed for the AIS 05 versus AIS 98. Changes in outcome measures for this stratum were as follows (AIS 98 versus AIS 05): mortality, 4.3% versus 7.7% (p=0.002); hospital length of stay, 5.2 days versus 7.3 days (p0.001); percent of patients not discharged home, 39.2% versus 49.3% (p0.001). Finally, there was a 20.5% reduction in patients with an ISSor=16 and a 26.2% reduction in patients with an ISSor=25 using the AIS 05.The AIS revision had a significant impact on overall injury severity measures, clinical outcome measures, and percent of patients in each ISS strata. Therefore, the AIS revision affects the ability to directly compare data generated using AIS 05 and AIS 98 which has implications in trauma research, reimbursement and ACS accreditation.

Background We previously hypothesized that the N-terminus of human serum albumin (HSA) is altered during ischemic events, thus establishing the foundation for the cobalt–HSA binding assay phenomenon. In this investigation, we attempt to clarify the mode of action of the cobalt–HSA binding assay by direct observations of cobalt binding to HSA. Methods High pressure liquid chromatography coupled to positive electrospray ionization mass spectrometry (HPLC/MS) was used to study cobalt binding to HSA in the plasma of patients with and without evidence of myocardial ischemia. Results Strong binding of cobalt to the N-terminus of HSA occurs at pH > 7.0. No differences in cobalt binding to the N-terminus of HSA are observed in ischemic versus non-ischemic patients' plasma despite differences in the cobalt–HSA binding assay. Plasma free cysteine/cystine ratio appears to play a role in the quantitative response of the cobalt–HSA binding assay. Conclusions The main determinants of the cobalt–HSA binding assay mechanism of action include but are not limited to: the proportion of intact N-terminus of HSA, HSA concentration, plasma cysteine/cystine ratio, plasma pH, and the state of oxidation of cys34 of HSA. Assay improvements that consider and take these factors into account could lead to an improved cobalt–HSA binding assay with greater clinical utility.

Objective To determine the effects of the androgen-like synthetic steroid, danazol, on endothelial cell function and angiogenesis. Design In vitro cell culture models were designed to investigate three critical steps involved in angiogenesis: endothelial cell proliferation, invasion, and tube formation. Setting Research laboratory at a level one trauma center. Patient(s) Commercially available human umbilical vein endothelial cells (HUVEC) were purchased from a pooled patient source. Intervention(s) The HUVEC cells were treated with danazol at concentrations ranging from 1 to 100 μM and evaluated using a series of angiogenesis assays. Main Outcome Measure(s) Absolute cells numbers were quantified using colorimetric methods and fluorescent dyes for cells exposed to danazol in both proliferation assays and invasion chambers. AngiQuant vl.33 software was used to evaluate the formation of capillary-like structures on extracellular matrix gels in the presence of danazol. Result(s) Endothelial cells scrutinized by our in vitro models exhibited decreased proliferation (up to 86%) and tube length (up to 115%) in the presence danazol. Cellular invasion through extracellular matrix, however, was not apparently affected by danazol under the conditions used. Conclusion(s) Danazol interfered with two of the three steps of angiogenesis studied in vitro. This data may help elucidate the mode of action for danazol in vivo.

Copper mobilization and subsequent redox reactions have been implicated in the pathogenesis of numerous inflammation-based diseases. Reduction of the cupric ion (Cu(2+)) to the cuprous ion (Cu(+)) is necessary for the production of copper-induced reactive oxygen species (ROS). Peptides, designed to bind both Cu(2+) and Cu(+) and have the ability to prevent copper redox reactions, were studied. The peptides DAHGMTCANC and DAHKGMTCANC were effective at preventing the formation of thiobarbituric acid-reactive species (TBARS) in a copper/ascorbate solution at a 1:1 peptide/Cu ratio. This was observed in the reducing potential of the copper/ascorbate solutions containing these peptides at a 1:1 ratio based on oxidation-reduction potential (ORP) measurements. The peptide DAHGMTCARC was effective at a 2:1 ratio, but not at a 1:1 ratio in which an increase in the oxidation potential was observed. This suggests that a positively charged amino acid such as arginine (R) in the Cu(+)-binding motif interferes with metal chelation. All peptides tested were effective at preventing IL-8 release from phorbol 12-myristate 13-acetate (PMA)/copper-stimulated human umbilical vein endothelial cells (HUVEC). The use of Cu(+)/Cu(2+)-binding peptides might be beneficial in the treatment of ROS-related diseases associated with copper.

Introduction Gaucher's disease (GD) is an inborn error, autosomal recessive lysosomal lipid storage disorder characterized by the lack of the enzyme glucocerebrosidase. We observed some abnormalities in the plasma of a traumatized patient with GD. Case Report We report of a traumatized patient with GD that developed a severe systemic immune response during the course of an extended hospital stay. Plasma paraoxonase (PON) activity was assayed and found to be extremely low possibly due to the existence of GD in this particular patient. Also, a potentially novel post-translational modification (PTM) of albumin was noticed in the patient's plasma that coincided with enzyme replacement therapy (ERT) with Cerezyme®. Conclusions The decreased plasma PON activity measured might be a contributive factor in the development of an accentuated systemic immune response in a traumatized patient with GD. A modified albumin species could serve as a biomarker for ERT in Gaucher patients.

Introduction Hypoalbuminemia is known to occur in critically ill patients and is associated with increased mortality. We observed a potentially novel, partial explanation for the hypoalbuminemia noticed in a severely traumatized patient. Case report We report of a severely, multi-system traumatized patient in whom hypoalbuminemia was present (1–2 g/dl). The plasma albumin (HSA) was analyzed by liquid chromatography/positive electrospray ionization mass spectrometry. A high percentage of a truncated albumin that lost its carboxy terminal amino acid leucine (HSA-L) associated with a 10-fold increase in plasma carboxypeptidase A (CPA) activity (R2 = 0.994) were found. We estimated the half life of this truncated albumin species to be Conclusions The increased CPA activity encountered following a traumatic event and subsequent rapid clearance of the resulting HSA-L from plasma might be a contributing factor to the hypoalbuminemia observed in the critically ill patients.

Albumin is an abundant plasma protein with multiple physiologic functions, and low serum albumin levels have been associated with increased mortality in hospitalized patients. In a retrospective matched-pair study, we investigated whether emergency department (ED) albumin levels predict delayed mortality for patients initially stabilized after blunt trauma. Fifty-one hospital non-survivors who died more than 24 h after admission to a trauma center ED were matched by Injury Severity Score, type and location of injury, age, and gender with 51 survivors. All patients had serum albumin levels determined upon arrival in the ED. The non-survivors had a significantly lower admission albumin of 3.1 g/dL compared to 3.5 g/dL for survivors. Patients with albumin levels < 3.4 g/dL were 2.5 times more likely to die compared to patients with normal albumin levels. These preliminary results indicate that initial hypoalbuminemia in blunt trauma patients is an independent predictor of delayed mortality, suggesting that these patients require continued clinical vigilance and an aggressive search for evolving complications.

Computational systems in the field of building technology are, at present, mainly employed as electronic catalogs for the retrieval of technological information (content providers). However, the massive amount of information associated with building design demands explicit knowledge about the way various information pieces relate one to another in order to be able to achieve an intelligent use of those resources through the design process. This gives rise to a strong need for computational systems that help not only to retrieve information (design content) but also to explain the relationships between the elements of technological information (design context). The research presented in this paper has developed a conceptual model for the representation of knowledge in building technology based on specific context related to the field. The model employed an associative formalism reflecting the logical connections between pertinent information units used in the technological design process. The model is termed ICPD which stands for: Issue, Concept, Pattern and Detail. This model is to be employed in implementing a computational system to support design in building technology.

Activated protein C (APC) is useful in the treatment of sepsis. Ischemia and acidosis, which often accompany sepsis, cause the release of copper from loosely bound sites. We investigated (i) whether physiological concentrations of copper inhibit APC anticoagulant activity and (ii) if any copper-induced APC inhibition is reversible by human serum albumin (HSA) or a high-affinity copper-binding analogue of the human albumin N-terminus, d-Asp-d-Ala-d-His-d-Lys (d-DAHK). APC activity after 30 min of incubation with CuCl2 (10 microM) was decreased 26% below baseline. HSA, both alone and when combined with various ratios of CuCl2, increased APC activity significantly above baseline. d-DAHK alone and 2:1 and 4:1 ratios of d-DAHK:CuCl2 also increased APC activity. APC contained 1.4 microM copper, which helps explain the increased APC activity with HSA and d-DAHK alone. These in vitro results indicate that copper inhibits APC activity and that albumin and d-DAHK reverse the copper-induced APC deactivation.

Both DNA and the telomeric sequence are susceptible to copper-mediated reactive oxygen species (ROS) damage, particularly damage attributed to hydroxyl radicals. In this study, ROS-induced DNA double strand breaks and telomere shortening were produced by exposure to copper and ascorbic acid. Asp-Ala-His-Lys (DAHK), a specific copper chelating tetrapeptide d-analog of the N-terminus of human albumin, attenuated DNA strand breaks in a dose dependent manner. d-DAHK, at a ratio of 4:1 (d-DAHKCu), provided complete protection of isolated DNA from double strand breaks and, at a ratio of 2:1 (d-DAHKCu), completely protected DNA in Raji cells exposed to copper/ascorbate. Southern blots of DNA treated with copper/ascorbate showed severe depletion and shortening of telomeres and Raji cell treated samples showed some conservation of telomere sequences. d-DAHK provided complete telomere length protection at a ratio of 2:1 (d-DAHKCu). The human albumin N-terminus analog, d-DAHK, protects DNA and telomeres against copper-mediated ROS damage and may be a useful therapeutic adjunct in ROS disease processes.

We initially observed a phenomenon of reduced in vitro binding of exogenous cobalt [Co(II)] to the N-terminus of human serum albumin (HSA) in emergency chest pain patients with early onset unstable angina and myocardial infarction. We then developed a colorimetric assay to measure cobalt-HSA binding and record the results in absorbance units (ABSU). In a preliminary clinical study of 139 emergency patients with acute chest pain, 99 patients with evidence of myocardial ischemia (Group 1) had elevated assay levels (mean ABSU +/- SD; 0.519 +/- 0.086) compared to 40 patients (Group 2) with no evidence of ischemia (0.316 +/- 0.092) (p < 0.00001). In Group 1, 95 of 99 (96.0%) patients had levels higher than a decision threshold of 0.400 ABSU and in Group 2, 37 of 40 (92.5%) samples had higher cobalt binding capacity (ABSU

Introduction Purple urinary bag syndrome (PUBS) is considered to be a benign condition observed in the urinary catheter and bag in some catheterized patients with urinary tract infections. This syndrome is usually reported to occur in alkaline urine. Case report We report of a catheterized patient with PUBS and slightly acidic urine (pH 6–6.5). A novel analysis method was developed using high pressure liquid chromatography and mass spectrometry (HPLC/MS) to detect compounds that are thought to be associated with PUBS. Urine, urinary sediment, and the plastic collection system were assayed and quantitated using these methods. The potential toxicity of one of these compounds, indoxyl sulfate, is discussed. Conclusions The presence of PUBS in a catheterized patient with slightly acidic urine is reported. A novel method for the analysis of chemical components of PUBS and the first direct confirmation of the presence of indigo in the urine sediment and collecting system are described.

Epinephrine is known to be rapidly oxidized during sepsis. Ischemia and acidosis, which often accompany sepsis, are associated with the release of weakly bound cupric ions from plasma proteins. We investigated whether copper promotes oxidation of epinephrine at both physiological and acidic pH and whether D-Asp-D-Ala-D-His-D-Lys (D-DAHK), a human albumin (HSA) N-terminus synthetic peptide with a high affinity for cupric ions, attenuates this oxidation. Epinephrine alone [100 microM] or with CuCl(2) [10 microM], and with CuCl(2) [10 microM] and D-DAHK [20 microM] at pH 7.4, 7.0, 6.5, and 6.0 were incubated for 1h at 37 degrees C. Epinephrine oxidation was measured by the spectrophotometric quantification of its oxidation product, adrenochrome. We found that adrenochrome increased, suggesting copper-induced oxidation of epinephrine. At pH 7.4, 7.0, 6.5, and 6.0, adrenochrome increased by 47%, 53%, 24%, and 6% above baseline, respectively. D-DAHK attenuated the copper-induced oxidation of epinephrine to baseline levels. These in vitro results indicate that copper-induced epinephrine oxidation is greatest at the physiological pH 7.4 as well as in severe acidosis, pH 7.0, and that D-DAHK completely inhibits this oxidation.

The effects of acute ethanol administration on acid-base balance and hemodynamic parameters were studied in a canine model. Ten mongrel dogs, anesthetized and maintained on a volume ventilator, underwent splenic artery ligation 30 minutes prior to study. Group A (N = 5) served as controls. Thirty minutes after drug administration, the animals underwent a 20-cc/kg hemorrhage over 15 minutes. Thirty minutes postphlebotomy, resuscitation was performed with the same volume of homologous blood. Acid-base and hemodynamic parameters were monitored over 3.5 hours. Ethanol levels peaked 60 minutes following administration at 207 +/- 13 mg%. During the entire study, no differences were observed in heart rate, pulmonary capillary wedge pressure, systemic vascular resistance index, pO2, or pCO2, between the two groups. Following hemorrhage, statistically significant decreases in pH, mean arterial pressure (MAP), cardiac index (CI), and left ventricular stroke work index (LVSWI) developed in group A compared to controls. Maximal disparity developed in pH (7.21 +/- 0.05 to 7.33 +/- 0.02, P0.01), MAP (67 +/- 11 v 110 +/- 9 torr, P0.01), CI (1.69 +/- 0.24 compared to 2.72 +/- 0.19 L/min/M2, and LVSWI (18.7 +/- 1.2 compared to 44.9 +/- 4.8 gr-meter/M2/beat, P0.01) at 60, 45, 30, and 75 minutes postphlebotomy. In this study, ethanol directly or indirectly caused an increased metabolic acidosis and myocardial depression in the post-hemorrhage period.

Starting from the extended Lie algebras generated by the Gauss-law constraints, and using the coadjoint-orbit method, we construct bosonized actions for anomalous gauge theories in two and four space-time dimensions. We show that the anomalous gauge algebras determine the anomalous part of the actions, but not the gauge invariant terms. These are generated by exact cocycles.

Purpose: in a previous randomized controlled study we showed the advantage of J-shaped over straight screw-in leads in the atrium. In the present study we compared J-shaped tined passive fixation (PF) to screw-in active fixation (AF) leads. Methods: two hundred consecutive patients (pts) were randomized to have either a Medtronic 5568 J-shaped screw-in atrial lead (AF group, n=97) or a Medtronic 5592 J-shaped tined lead (PF group, n=103) implanted in the atrium. We documented implant data and electrical measurements at implant, pre-discharge, 3 months and one year; echocardiography and chest X-ray were performed at one day post implantation. All implant and follow-up complications were documented. Results: two hundred pts were included (103 males), aged 75.44-10.4, EF = 53 4- 11, of whom 39 (19.5%) had previously undergone cardiac surgery. In 5 cases (4 with a PF and one with an AF lead, P = 0.39), there was crossover to the alternate lead at implant due to inability to achieve a satisfactory position. Fluoroscopy times were shorter with PF: 2.14-3.6 vs. 3.3 4- 4.5 min (P=0.04). Bipolar electrical measurements are listed in the table. Lead Implant Pre-discharge 3 months One year 5568 (AF) Pwave mVoks 4.2±2.1 3.1±1.5 3.0±1.5 3.0±1.4 Impedance Ohm 434±133 533±126 531±142 529±139 Threshold Voks 0.9±0.3* 0.8±0.4* 1.2±0.7" 1.3±0.9" 5592 (PF) P wave mVoks 4.8±2.2 3.3±1.4 3.3±1.4 3.2±1.4 Impedance Ohm 448±100 476±88 498±84 500±77 Threshold Voks 0.7±0.5* 0.6±0.3* 0.7±0.6* 0.8±0.6* *P

A hodograph-vector-control concept is applied to the optimization of variable sweep in maneuvering flight. For a flight-control mode which is basically manual, with only the sweep control adjusted automatically as a function of flight conditions and the conventional flight controls, the hodograph approach leads to sweep commands dependent on Mach number, lift coefficient, and throttle/speed- brake setting. Some computations for an example are presented.

The ability of lavage alkaline phosphatase (LAP) to detect small intestinal injury was studied in 81 patients who underwent diagnostic peritoneal lavage following blunt and penetrating abdominal trauma. Patients with a grossly positive lavage were excluded. The LAP of five patients with small intestinal injury (79.0 +/- 41.7 IU/L) was significantly greater than in 76 cases without (1.2 +/- 0.4 IU/L; P less than .05). LAP greater than or equal to 3 was seen in six patients. Four had isolated small intestinal pathology, and one had combined small and large bowel injury. In three of these five, other lavage values were normal. One possible false positive occurred. The sensitivity of LAP greater than or equal to 3 (100%) exceeded that of usual lavage parameters in the detection of small intestinal injury. LAP may be a sensitive marker for small intestinal pathology in the immediate postinjury period.

The value of lavage alkaline phosphatase determinations following hollow visceral injury was studied. Twenty-nine mongrel dogs were subjected to partial transection of the small intestine or colon, or underwent sham laparotomy. Sequential diagnostic peritoneal lavage was performed. At one hour post injury the lavage red cell count, white cell count, and amylase levels were within normal limits in each group. The lavage alkaline phosphatase, however, was markedly elevated in both bowel-injured groups compared with the sham group. In the five-hour lavage, red cell counts and amylase levels remained normal. White cell counts were now elevated in all three groups, but the results did not distinguish the intestinal injury from the sham model. Lavage alkaline phosphatase was again significantly increased in the injured groups versus the sham model. Serum alkaline phosphatase and amylase levels were normal in all study groups at baseline and one and five hours post injury. This canine study demonstrates the utility of peritoneal lavage alkaline phosphatase levels in identifying isolated small intestine and colon injuries that were otherwise undetected by red cell, white cell, and amylase determinations.