Showing papers by "United States Department of the Army published in 2003"

Climate as a moderator of the relationship between leader-member exchange and content specific citizenship: safety climate as an exemplar.

Abstract: The present study integrates role theory, social exchange, organizational citizenship, and climate research to suggest that employees will reciprocate implied obligations of leadership-based social exchange (e.g., leader-member exchange [LMX]) by expanding their role and behaving in ways consistent with contextual behavioral expectations (e.g., work group climate). Using safety climate as an exemplar, the authors found that the relationship between LMX and subordinate safety citizenship role definitions was moderated by safety climate. In summary, high-quality LMX relationships resulted in expanded safety citizenship role definitions when there was a positive safety climate and there was no such expansion under less positive safety climates. The authors also found that safety citizenship role definitions were significantly related to safety citizenship behavior. Implications for both social exchange theory and safety research are discussed.

Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection.

Abstract: Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined sequentially over a 6-day period to investigate the pathological events of EBOV infection that lead to death. Importantly, dendritic cells in lymphoid tissues were identified as early and sustained targets of EBOV, implicating their important role in the immunosuppression characteristic of EBOV infections. Bystander lymphocyte apoptosis, previously described in end-stage tissues, occurred early in the disease-course in intravascular and extravascular locations. Of note, apoptosis and loss of NK cells was a prominent finding, suggesting the importance of innate immunity in determining the fate of the host. Analysis of peripheral blood mononuclear cell gene expression showed temporal increases in tumor necrosis factor-related apoptosis-inducing ligand and Fas transcripts, revealing a possible mechanism for the observed bystander apoptosis, while up-regulation of NAIP and cIAP2 mRNA suggest that EBOV has evolved additional mechanisms to resist host defenses by inducing protective transcripts in cells that it infects. The sequence of pathogenetic events identified in this study should provide new targets for rational prophylactic and chemotherapeutic interventions.

Reliability and diagnostic accuracy of the clinical examination and patient self-report measures for cervical radiculopathy.

Abstract: STUDY DESIGN: A blinded, prospective diagnostic test study was conducted. OBJECTIVES: To assess the reliability and accuracy of individual clinical examination items and self-report instruments for the diagnosis of cervical radiculopathy, and to identify and assess the accuracy of an optimum test-item cluster for the diagnosis of cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Although cervical radiculopathy remains largely a clinical diagnosis, the reliability and diagnostic accuracy of clinical examination items, individually or in combination, for cervical radiculopathy is largely unknown. METHODS: Patients with suspected cervical radiculopathy or carpal tunnel syndrome received standardized electrophysiologic examination of the symptomatic upper quarter followed by a standardized clinical examination by physical therapist examiners blinded to diagnosis. Diagnostic properties were assessed using a neural impairment reference criterion standard. RESULTS: The study involved 82 patients. More than two thirds of 34 clinical examination items had reliability coefficients rated at least fair or better, and 13 items had likelihood ratio point estimates above 2 or below 0.50. A single diagnostic test item cluster of four variables was identified and produced a positive likelihood ratio point estimate of 30.3. The 95% confidence intervals for all likelihood ratio point estimates in this study were wide. CONCLUSIONS: Many items of the clinical examination were found to be reliable and to have acceptable diagnostic properties, but the test item cluster identified was more useful for indicating cervical radiculopathy than any single test item. Upper limb tension Test A was the most useful test for ruling out cervical radiculopathy. Further investigation is required both to validate the test item cluster and to improve point estimate precision.

Removal of hexavalent chromium from wastewater using a new composite chitosan biosorbent.

Abstract: A new composite chitosan biosorbent was prepared by coating chitosan, a glucosamine biopolymer, onto ceramic alumina. The composite bioadsorbent was characterized by high-temperature pyrolysis, porosimetry, scanning electron microscopy, and X-ray photoelectron spectroscopy. Batch isothermal equilibrium and continuous column adsorption experiments were conducted at 25 degrees C to evaluate the biosorbent for the removal of hexavalent chromium from synthetic as well as field samples obtained from chrome plating facilities. The effect of pH, sulfate, and chloride ion on adsorption was also investigated. The biosorbent loaded with Cr(VI) was regenerated using 0.1 M sodium hydroxide solution. A comparison of the results of the present investigation with those reported in the literature showed that chitosan coated on alumina exhibits greater adsorption capacity for chromium(VI). Further, experimental equilibrium data were fitted to Langmuir and Freundlich adsorption isotherms, and values of the parameters of the isotherms are reported. The ultimate capacity obtained from the Langmuir model is 153.85 mg/g chitosan.

The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3

Abstract: The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza virus IFN antagonist protein, NS1. The Ebola virus VP35 could also prevent the virus- or double-stranded RNA-mediated transcriptional activation of both the beta IFN (IFN-β) promoter and the IFN-stimulated ISG54 promoter (C. Basler et al., Proc. Natl. Acad. Sci. USA 97:12289-12294, 2000). We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-α/β receptor. The ability of VP35 to inhibit this virus-induced transcription correlates with its ability to block activation of IRF-3, a cellular transcription factor of central importance in initiating the host cell IFN response. We demonstrate that VP35 blocks the Sendai virus-induced activation of two promoters which can be directly activated by IRF-3, namely, the ISG54 promoter and the ISG56 promoter. Further, expression of VP35 prevents the IRF-3-dependent activation of the IFN-α4 promoter in response to viral infection. The inhibition of IRF-3 appears to occur through an inhibition of IRF-3 phosphorylation. VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation. Consistent with these observations, Ebola virus infection of Vero cells activated neither transcription from the ISG54 promoter nor nuclear accumulation of IRF-3. These data suggest that in Ebola virus-infected cells, VP35 inhibits the induction of antiviral genes, including the IFN-β gene, by blocking IRF-3 activation.

Obstructive Sleep-Related Breathing Disorders in Patients Evaluated for Bariatric Surgery

Abstract: Background: Obesity is a well known risk factor for obstructive sleep apnea (OSA). Medical therapy is not effective for morbid obesity. Bariatric surgery is therefore a reasonable option for weight reduction for patients with clinically severe obesity. Unrecognized OSA, especially in those patients receiving abdominal surgery, has influenced perioperative morbidity and morality. The incidence of OSA for patients being evaluated for bariatric surgery has not been previously defined. Methods: 40 consecutive patients being evaluated for bariatric surgery were examined with a history, physical examination and laboratory data. Polysomnography (PSG) was conducted in all patients regardless of symptoms. Results: An obstructive sleep-related breathing disorder (OSRBD) was present in 88% of the patients. OSA was present in 29 of 41 (71%) and upper airway resistance syndrome (UARS) in 7 of 41 (17%). The mean low oxygen desaturation was 84% and continuous positive airway pressure (CPAP) was 10 cm H2O pressure. The majority of the patients were women and mean BMI was 47 kg/m2. Patient characteristics failed to predict the severity of OSRBD. Conclusions: This population of clinically severe obese patients being evaluated for bariatric surgery had an 88% incidence of an OSRBD, 71% with OSA. Appropriate therapy with CPAP perioperatively would theoretically prevent hypoxic complications associated with OSRBD. Providers should have a low threshold for ordering a PSG as part of the preoperative evaluation for bariatric surgery. Empiric CPAP at 10 cm H2O should be considered for those patients who cannot complete a PSG before surgery.

Vitamin B12 deficiency.

Abstract: Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels; however, about 50 percent of patients with subclinical disease have normal B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorption of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective.

Fluid balance and endurance exercise performance

Abstract: Dehydration alters cardiovascular, thermoregulatory, central nervous system, and metabolic functions. One or more of these alterations will degrade endurance exercise performance when dehydration exceeds 2% of body weight. These performance decrements are accentuated by heat stress. To minimize the adverse consequences of body water deficits on endurance exercise performance, it is recommended that fluid intake be sufficient to minimize dehydration to less than 2% of body weight loss. This can usually be achieved with fluid intakes of under 1 L x h(-1).

Effect of a chitosan-based hemostatic dressing on blood loss and survival in a model of severe venous hemorrhage and hepatic injury in swine.

Abstract: : Background: Hemorrhage is a leading cause of death from trauma. An advanced hemostatic dressing could aug- ment available hemostatic methods. We studied the effects of a new chitosan dressing on blood loss, survival, and fluid use after severe hepatic injury in swine. Methods: Swine received chitosan dressings or gauze sponges. Standardized, severe liver injuries were induced. After 30 seconds, dressings were applied and resuscitation initiated. Blood loss, hemostasis, resuscitation volume, and 60- minute survival were quantified. Results: Posttreatment blood loss was reduced ( p less than 0.01) in the chitosan group (264 mL; 95% confidence interval [CI], 82 852 mL) compared with the gauze group (2,879 mL; 95% CI, 788 10,513 mL). Fluid use was reduced (p = 0.03) in the chitosan group (1,793 mL; 95% CI, 749 4,291) compared with the gauze group (6,614 mL; 95% CI, 2,519 17,363 mL). Survival was seven of eight and two of even in the chitosan and gauze groups ( p = 0.04), respectively. Hemostasis was improved in the chitosan group (p = 0.03). Conclusion: A chitosan dressing reduced hemorrhage and improved survival after severe liver injury in swine. Further studies are warranted.

Myopericarditis Following Smallpox Vaccination Among Vaccinia-Naive US Military Personnel

Abstract: ContextIn the United States, the annual incidence of myocarditis is estimated at 1 to 10 per 100 000 population. As many as 1% to 5% of patients with acute viral infections involve the myocardium. Although many viruses have been reported to cause myopericarditis, it has been a rare or unrecognized event after vaccination with the currently used strain of vaccinia virus (New York City Board of Health).ObjectiveTo describe a series of probable cases of myopericarditis following smallpox vaccination among US military service members reported since the reintroduction of vaccinia vaccine.Design, Setting, ParticipantsSurveillance case definitions are presented. The cases were identified either through sentinel reporting to US military headquarters surveillance using the Defense Medical Surveillance System or reports to the Vaccine Adverse Event Reporting System using International Classification of Diseases, Ninth Revision. The cases occurred among individuals vaccinated from mid-December 2002 to March 14, 2003.Main Outcome MeasureElevated serum levels of creatine kinase (MB isoenzyme), troponin I, and troponin T, usually in the presence of ST-segment elevation on electrocardiogram and wall motion abnormalities on echocardiogram.ResultsAmong 230 734 primary vaccinees, 18 cases of probable myopericarditis after smallpox vaccination were reported (an incidence of 7.8 per 100 000 over 30 days). No cases of myopericarditis following smallpox vaccination were reported among 95 622 vaccinees who were previously vaccinated. All cases were white men aged 21 years to 33 years (mean age, 26.5 years), who presented with acute myopericarditis 7 to 19 days following vaccination. A causal relationship is supported by the close temporal clustering (7-19 days; mean, 10.5 days following vaccination), wide geographic and temporal distribution, occurrence in only primary vaccinees, and lack of evidence for alternative etiologies or other diseases associated with myopericarditis. Additional supporting evidence is the observation that the observed rate of myopericarditis among primary vaccinees is 3.6-fold (95% confidence interval, 3.33-4.11) higher than the expected rate among personnel who were not vaccinated. The background incidence of myopericarditis did not show statistical significance when stratified by age (20-34 years: 2.18 expected cases per 100 000; 95% confidence interval [CI], 1.90-2.34), race (whites: 1.82 per 100 000; 95% CI, 1.50-2.01), and sex (males: 2.28 per 100 000; 95% CI, 2.04-2.54).ConclusionAmong US military personnel vaccinated against smallpox, myopericarditis occurred at a rate of 1 per 12 819 primary vaccinees. Myopericarditis should be considered an expected adverse event associated with smallpox vaccination. Clinicians should consider myopericarditis in the differential diagnosis of patients presenting with chest pain 4 to 30 days following smallpox vaccination and be aware of the implications as well as the need to report this potential adverse advent.

Pathogenesis of Ebola Hemorrhagic Fever in Primate Models: Evidence that Hemorrhage Is Not a Direct Effect of Virus-Induced Cytolysis of Endothelial Cells

Abstract: Ebola virus (EBOV) infection causes a severe and often fatal hemorrhagic disease in humans and nonhuman primates. Whether infection of endothelial cells is central to the pathogenesis of EBOV hemorrhagic fever (HF) remains unknown. To clarify the role of endothelial cells in EBOV HF, we examined tissues of 21 EBOV-infected cynomolgus monkeys throughout time, and also evaluated EBOV infection of primary human umbilical vein endothelial cells and primary human lung-derived microvascular endothelial cells in vitro. Results showed that endothelial cells were not early cellular targets of EBOV in vivo, as viral replication was not consistently observed until day 5 after infection, a full day after the onset of disseminated intravascular coagulation. Moreover, the endothelium remained relatively intact even at terminal stages of disease. Although human umbilical vein endothelial cells and human lung-derived microvascular endothelial cells were highly permissive to EBOV replication, significant cytopathic effects were not observed. Analysis of host cell gene response at 24 to 144 hours after infection showed some evidence of endothelial cell activation, but changes were unremarkable considering the extent of viral replication. Together, these data suggest that coagulation abnormalities associated with EBOV HF are not the direct result of EBOV-induced cytolysis of endothelial cells, and are likely triggered by immune-mediated mechanisms.

Overlapping Motifs (PTAP and PPEY) within the Ebola Virus VP40 Protein Function Independently as Late Budding Domains: Involvement of Host Proteins TSG101 and VPS-4

Abstract: The VP40 protein of Ebola virus can bud from mammalian cells in the form of lipid-bound, virus-like particles (VLPs), and late budding domains (L-domains) are conserved motifs (PTAP, PPxY, or YxxL; where "x" is any amino acid) that facilitate the budding of VP40-containing VLPs. VP40 is unique in that potential overlapping L-domains with the sequences PTAP and PPEY are present at amino acids 7 to 13 of VP40 (PTAPPEY). L-domains are thought to function by interacting with specific cellular proteins, such as the ubiquitin ligase Nedd4, and a component of the vacuolar protein sorting (vps) pathway, tsg101. Mutational analysis of the PTAPPEY sequence of VP40 was performed to understand further the contribution of each individual motif in promoting VP40 budding. In addition, the contribution of tsg101 and a second member of the vps pathway, vps4, in facilitating budding was addressed. Our results indicate that (i) both the PTAP and PPEY motifs contribute to efficient budding of VP40-containing VLPs; (ii) PTAP and PPEY can function as L-domains when separated and moved from the N terminus (amino acid position 7) to the C terminus (amino acid position 316) of full-length VP40; (iii) A VP40-PTAP/tsg101 interaction recruits tsg101 into budding VLPs; (iv) a VP40-PTAP/tsg101 interaction recruits VP40 into lipid raft microdomains; and (v) a dominant-negative mutant of vps4 (E228Q), but not wild-type vps4, significantly inhibited the budding of Ebola virus (Zaire). These results provide important insights into the complex interplay between viral and host proteins during the late stages of Ebola virus budding.

Ebola virus-like particles protect from lethal Ebola virus infection

Abstract: The filovirus Ebola causes hemorrhagic fever with 70–80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (VP40) in mammalian cells results in spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. VLPs have been tested and found efficacious as vaccines for several viruses, including papillomavirus, HIV, parvovirus, and rotavirus. Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor α by the dendritic cells. Further, vaccinating mice with eVLPs activated CD4+ and CD8+ T cells, as well as CD19+ B cells. After vaccination with eVLPs, mice developed high titers of Ebola virus-specific antibodies, including neutralizing antibodies. Importantly, mice vaccinated with eVLPs were 100% protected from an otherwise lethal Ebola virus inoculation. Together, our data suggest that eVLPs represent a promising vaccine candidate for protection against Ebola virus infections and a much needed tool to examine the genesis and nature of immune responses to Ebola virus.

Higher-order cyclic cumulants for high order modulation classification

Abstract: In this paper we investigate automatic modulation classification (AMC) using homogeneous feature-vectors based on cyclic cumulants (CCs) of fourth-, sixth- and eight-orders, respectively, for QAM, PSK and ASK signals within a pattern recognition framework. Analysis of CCs of the baseband signal at the receiver is performed and used for feature selection. The cycle spectrum of the baseband signal at the receiver is derived as a function of excess bandwidth for a raised cosine pulse shape and a necessary and sufficient condition on the oversampling factor is obtained. Theoretical arguments regarding the discrimination capability of the examined feature-vectors are verified through extensive simulations.

Application of fiber reinforced polymer overlays to extend steel fatigue life

Abstract: An experimental and analytical study was conducted to investigate the effectiveness of applying carbon fiber reinforced polymer (CFRP) overlays to steel fatigue tension coupons to prolong fatigue life. Specimens were either notched or center hole specimens and tested in uniaxial tension. Variables studied were CFRP system, bond length, bond area, one and two sided applications, and applications prior or subsequent to crack propagation. Two sided applications were very effective, prolonging fatigue life by as much as 115%. Similar application of CFRP materials subsequent to crack propagation extended the remaining fatigue life by approximately 170% without any other means of crack arrest. The method therefore showed promise as both a preventive technique and repair method. The epoxy performance was critical to the effectiveness of the system, with all failures initiated by debonding of the CFRP. Overlays were most effective when the system was applied directly to the potential crack trajectory. One-sided a...

THz-Spectroscopy of Biological Molecules.

Abstract: The terahertz frequency absorption spectraof DNA molecules reflect low-frequencyinternal helical vibrations involvingrigidly bound subgroups that are connectedby the weakest bonds, including thehydrogen bonds of the DNA base pairs,and/or non-bonded interactions. Althoughnumerous difficulties make the directidentification of terahertz phonon modes inbiological materials very challenging, ourresearch has shown that such measurementsare both possible and fruitful. Spectra ofdifferent DNA samples reveal a large numberof modes and a reasonable level ofsequence-specific uniqueness. In an attemptto show that the long wavelength absorptionfeatures are intrinsic properties ofbiological materials determined by phononmodes, a normal mode analysis has been usedto predict the absorption spectra ofpolynucleotide RNA Poly[G]-Poly[C]. Directcomparison demonstrated a correlationbetween calculated and experimentallyobserved spectra of the RNA polymers, thusconfirming that the fundamental physicalnature of the observed resonance structureis caused by the internal vibration modesin the macromolecules.In this work we demonstrate results fromFourier-Transform Infrared (FTIR)spectroscopy of DNA macromolecules andrelated biological materials in theterahertz frequency range. Carefulattention was paid to the possibility ofinterference or etalon effects in thesamples, and phenomena were clearlydifferentiated from the actual phononmodes. In addition, we studied thedependence of transmission spectra ofaligned DNA and polynucleotide film sampleson molecule orientation relative to theelectromagnetic field, showing the expectedchange in mode strength as a function ofsample orientation. Further, the absorptioncharacteristics were extracted from thetransmission data using the interferencespectroscopy technique, and a stronganisotropy of terahertz characteristics wasdemonstrated.

Stabilization of Clay Soils with Nontraditional Additives

Abstract: A laboratory experiment was conducted to evaluate the stabilization of low- and high-plasticity clay soils with nontraditional chemical or liquid stabilizers. Clay soil specimens were mixed with various stabilization products and compacted using a gyratory compaction machine to approximate ASTM D1557 moisture—density compaction. Each specimen was subjected to wet and dry testing following a 28-day cure. Twelve nontraditional stabilizers were evaluated, including an acid, enzymes, a lignosulfonate, a petroleum emulsion, polymers, and a tree resin. Additional specimens were stabilized with Type I portland cement and hydrated lime for comparison with traditional stabilizers under the same mixing, compaction, and curing conditions. Analysis of the test data consisted of determining the average strength, in terms of unconfined compressive strength, of three replicate specimens of each mixture. The average strength of the three replicates of each additive was compared with the average strength results of the re...

US military smallpox vaccination program experience.

Abstract: Context The United States recently implemented smallpox vaccination of selected military personnel in a national program of preparedness against use of smallpox as a biological weapon. The resumption of smallpox vaccinations raises important questions regarding implementation and safety. Objective To describe the US military smallpox vaccination program. Design Descriptive study of the vaccination program from its inception on December 13, 2002, through May 28, 2003. Setting US Department of Defense (DoD) fixed and field medical treatment facilities on multiple continents and ships at sea. Subjects US service members and DoD civilian workers eligible for smallpox vaccination. Main outcome measures Numbers of vaccinations and rates of vaccination exemptions, symptoms, and adverse events. Data were collected via reports to headquarters and rigorous surveillance for sentinel events. Results In 5.5 months, the DoD administered 450 293 smallpox vaccinations (70.5% primary vaccinees and 29.5% revaccinees). In 2 settings, 0.5% and 3.0% of vaccine recipients needed short-term sick leave. Most adverse events occurred at rates below historical rates. One case of encephalitis and 37 cases of acute myopericarditis developed after vaccination; all cases recovered. Among 19 461 worker-months of clinical contact, there were no cases of transmission of vaccinia from worker to patient, no cases of eczema vaccinatum or progressive vaccinia, and no attributed deaths. Conclusions Mass smallpox vaccinations can be conducted safely with very low rates of serious adverse events. Program implementation emphasized human factors: careful staff training, contraindication screening, recipient education, and attention to bandaging. Our experience suggests that broad smallpox vaccination programs may be implemented with fewer serious adverse events than previously believed.

Ribavirin Causes Error Catastrophe during Hantaan Virus Replication

Abstract: Except for ribavirin, no other antiviral drugs for treating hantaviral diseases have been identified. It is well established that ribavirin will inhibit the production of infectious Hantaan virus (HTNV); however, its mechanism of action is unknown. To characterize the inhibitory effect of ribavirin on HTNV, the levels of viral RNAs, proteins, and infectious particles were measured for 3 days posttreatment of HTNV-infected Vero E6 cells. HTNV-infected cells treated with ribavirin showed a slight reduction in the levels of cRNA, viral RNA, and mRNA populations on the first day postinfection. The amount of cRNA and viral RNA increased to that observed for untreated HTNV-infected cells on day 2, whereas mRNA levels were more greatly reduced on days 2 and 3. Despite the finding of S-segment mRNA, albeit low, three of the viral proteins—nucleocapsid (N) protein and glycoproteins G1 and G2—could not be detected by immunohistochemistry in ribavirin-treated cells. To test the hypothesis that these effects were caused by incorporation of ribavirin into nascent RNA and a resultant “error catastrophe” was occurring, we cloned and sequenced the S-segment cRNA/mRNA from ribavirin-treated or untreated cells from day 3. We found a high mutation frequency (9.5/1,000 nucleotides) in viral RNA synthesized in the presence of ribavirin. Hence, the transcripts produced in the presence of the drug were not functional. These results suggest that ribavirin's mechanism of action lies in challenging the fidelity of the hantavirus polymerase, which causes error catastrophe.

Blood pressure at which rebleeding occurs after resuscitation in swine with aortic injury.

Abstract: : Background: The appropriateness of vigorous fluid resuscitation to normal blood pressure following hemorrhage in uncontrolled bleeding has recently been questioned due to the possibility of dislodging clots and exacerbating hemorrhage. To develop a rational blood pressure target that maximizes the metabolic benefits of resuscitation without causing increased blood loss, it was first necessary to determine whether there is a reproducible mean arterial pressure (MAP) at which rebleeding occurs. The purpose of this study was to explore the relationship between the rate and time of resuscitation after injury and the rebleeding MAP in an uncontrolled hemorrhage model. Methods: Sixty-two anesthetized pigs were instrumented with catheters and splenectomized, and suction tubes were placed in the lateral peritoneal recesses to continuously capture shed blood. With the abdomen open, an aortotomy was made in the infrarenal aorta. At either 5, 15, or 30 minutes after the end of the initial hemorrhage, resuscitation with warmed lactated Ringer s solution was begun at either 100 or 300 mL/min. The rebleeding MAP was determined at the moment blood appeared in the suction tubes. Results: The average pressure at the rebleeding point for all animals was MAP 64 + or - 2, Systolic 94+ or - 3, and Diastolic 45 + or - 2 mm Hg. The pressure at which rebleeding occurred in this aortotomy model was not affected by either time of resuscitation (5-30 min), nor was the rebleeding pressure affected by the rate (100 vs. 300 mL/min) of resuscitation. Conclusions: There was a reproducible pressure at which rebleeding occurred in this model of uncontrolled hemorrhage. The optimal endpoint of resuscitation in patients without definitive hemorrhage control would then be below this rebleeding pressure.

Comparison of 10 Different Hemostatic Dressings in an Aortic Injury

Abstract: : Background: Uncontrolled hemorrhage is the leading preventable cause of death on the battlefield. Similarly, hemorrhage accounts for 80% of all deaths within the first 48 hours of injury in civilian trauma patients. New methods of hemostasis are required to reduce hemorrhagic mortality. The purpose of this study was to compare nine hemostatic dressings for their efficacy in controlling bleeding from an otherwise fatal aortic injury in a pig model. Each hemostatic dressing was compared with the current standard U.S. Army field gauze dressing for a 1-hour period. Methods: Fifty-nine anesthetized pigs were instrumented with catheters and splenectomized. Nine test dressings (n = 5 per group) and two control groups (gauze, n = 9; suture, n = 5) were applied to a 4.4-mm aortotomy through the spraying jet of blood, and direct pressure was held for 4 minutes and then released. Survival, blood loss, and other variables were measured over a 1-hour period. Results: All animals with fibrin dressing and those receiving suture repair (five of five in both groups) survived the 1-hour observation period with minimal bleeding in the postocclusion period (less than 37 mL). Those in the other dressing groups exsanguinated within 10 minutes, except for two animals in the gauze group surviving 1 hour. Conclusion: With one 4-minute application, a single fibrin dressing stopped bleeding from an aortotomy, which was equivalent to sutured repair. No other test group exhibited any evidence of significant hemostatic efficacy.