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Study objective The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. Methods We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. Results The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. Conclusion Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Torpor is an important physiological process used to reduce body temperature and thus energy needs in mammals and birds. Rewarming from torpor can be costly. In some small mammals basking is used to reduce the cost of rewarming from torpor. The use and duration of basking was measured in two native Australian marsupials, the red-tailed phascogale (Phascogale calura) and kultarr (Antechinomys laniger), using a heat rock. Animals were observed via video cameras to determine whether they used basking behaviours and whether this behaviour was affected by food availability. Both species became accustomed to the heat rock as time progressed. Absence of food increased basking duration and frequency in some individuals but not all animals. Generally kultarrs basked for longer periods than phascogales, and kultarrs would bask at all hours of the day while phascogales showed a strict nocturnal regime (1900-0700h). The results demonstrate that basking may be an important behavioural adaptation of the kultarr; while the phascogale requires further research.

Patients suffering traumatic brain and chest wall injuries are often difficult to liberate from the ventilator yet best timing of tracheostomy remains ill-defined. While prior studies have addressed early versus late tracheostomy, they generally suffer from the use of historical controls, which cannot account for variations in management over time. Propensity scoring can be utilized to identify controls from the same patient population, minimizing impact of confounding variables. The purpose of this study was to determine outcomes associated with early versus late tracheostomy by application of propensity scoring.Patients requiring intubation within 48h and receiving tracheostomy from January 2010 to June 2012 were identified. Early tracheostomy (ET) was a tracheostomy performed by the fifth hospital day. ET patients were matched to late tracheostomy patients (LT, tracheostomy after day 5) using propensity scoring and compared for multiple outcomes. Cost for services was calculated using average daily billing rates at our institution.One hundred and six patients were included, 53 each in the ET (mean day tracheostomy=4) and the LT (mean day tracheostomy=10) cohorts. The average age was 47 years and 94% suffered blunt injury, with an average NISS of 23.7. Patients in the ET group had significantly shorter TICU LOS (21.4 days vs. 28.6 days, p0.0001) and significantly fewer ventilator days (16.7 days vs. 21.9, p0.0001) compared to the LT group. ET patients also had significantly less VAP (34% vs. 64.2%, p=0.0019).In the current era of increased health-care costs, early tracheostomy significantly decreased both pulmonary morbidity and critical care resource utilization. This translates to an appreciable cost savings, at minimum $52,173 per patient and a potential total savings of $2.8million/year for the entire LT cohort. For trauma patients requiring prolonged ventilator support, early tracheostomy should be performed.

Background Achieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy. Methods Patients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge. Results One hundred ninety-two patients were enrolled (epoetin alfa [n = 97], placebo [n = 95]). Hb increased from baseline to hospital discharge in both groups (epoetin alfa: 1.2 g/dL vs placebo: 0.9 g/dL), and transfusion requirements were similar between groups. Both groups showed improvements in SF-36 PF; there were no significant differences in the average of all posthospital discharge scores (epoetin alfa: 27.3 vs placebo 30.9; P = 0.38). Thromboembolic events were similar between groups. Conclusions No differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.

Since the advent of damage control surgery, more patients are left with an open abdomen. Surgeons are then left with the challenge of how to restore continuity of the abdominal wall. Many different techniques have been utilized for reconstruction with widely variable recurrence rates, mainly depending on the length of follow-up. A modification of the components separation technique was developed in Memphis, Tennessee at the Presley Memorial Trauma Center. This modification greatly increased the length gained in the midline. Additionally, many patients can be reconstructed without the use of prosthetics, reducing the infectious complications. The purpose of this manuscript is to describe in detail how to perform a modification of the components separation technique that has been shown to have one of the lowest recurrence rates in the literature.

Summary Background Occult diaphragmatic injury following penetrating thoracoabdominal trauma can be difficult to diagnose. Radiographic findings are often non-specific or absent. Undetected injuries may remain clinically silent, only to present later with life-threatening complications associated with diaphragmatic herniation. Diagnostic laparoscopy allows for the evaluation of trauma patients lacking clinical indications for a formal laparotomy. The purpose of this study was to evaluate the incidence of occult diaphragmatic injury and investigate the role of laparoscopy in patients with penetrating thoracoabdominal trauma who lack indications for exploratory laparotomy except the potential for a diaphragmatic injury. Methods Haemodynamically stable patients with penetrating thoracoabdominal trauma without indications for laparotomy (haemodynamic instability, evisceration, or peritonitis on exam) and evaluated with diagnostic laparoscopy to determine the presence of a diaphragmatic injury were retrospectively reviewed. Thoracoabdominal wounds were defined as wounds bounded by the nipple line over the anterior and posterior chest superiorly and the costal margin inferiorly. Results One hundred and eight patients were evaluated for penetrating thoracoabdominal injuries (80 stabs and 28 gunshots) over the study period. 22 (20%) diaphragmatic injuries were identified. These were associated with injuries to the spleen (5), stomach (3) and liver (2). There was a greater incidence of haemopneumothorax (HPTX) in patients with diaphragmatic injury (32%) compared to those without injury (20%). 29% of patients with a HPTX had a diaphragmatic injury. However, 18% of patients with a normal chest radiograph were also found to have a diaphragmatic injury. Conclusions The incidence of diaphragmatic injury associated with penetrating thoracoabdominal trauma is high. Clinical and radiographic findings can be unreliable for detecting occult diaphragmatic injury. Diagnostic laparoscopy provides a vital tool for detecting occult diaphragmatic injury among patients who have no other indications for formal laparotomy.

Damage control surgery is fundamental to operative trauma care. Prophylactic application of open abdomen techniques has led to avoidance of a great deal of the organ dysfunction associated with abdominal compartment syndrome. Surgeons are learning about management of large open abdominal wounds. There seems to be a general consensus regarding acute management of these wounds. Institutions are using staged techniques of management. Getting open wounds closed as soon as possible leads to fewer complications. The acute use of vacuum wound may provide for early secondary closure. There is less study focused on optimal definitive reconstructive techniques. Further study in all of these areas will lead to improved outcomes.

We review the X-ray spectra of the cores of clusters of galaxies. Recent high resolution X-ray spectroscopic observations have demonstrated a severe deficit of emission at the lowest X-ray temperatures as compared to that expected from simple radiative cooling models. The same observations have provided compelling evidence that the gas in the cores is cooling below half the maximum temperature. We review these results, discuss physical models of cooling clusters, and describe the X-ray instrumentation and analysis techniques used to make these observations. We discuss several viable mechanisms designed to cancel or distort the expected process of X-ray cluster cooling., To appear in Physics Reports, 71 pages, 20 figures

ObjectiveWe tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model.MethodsRapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration.ResultsAll animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P < .0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P = .0007) when compared with the other two groups by using two-tailed Student t tests. There was no evidence of medial necrosis or aneurysmal degeneration. All patent grafts had complete endothelialization on hematoxylin and eosin sections. Rapamycin was detectable and quantifiable in the arterial wall at 28 days after implantation.ConclusionsRapamycin can be coated onto and eluted from ePTFE by using a nonionic polymer and a simple coating technique. At 4 weeks after implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with non–drug-eluting ePTFE. Four weeks after implantation in a porcine model, rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with untreated and adhesive-only coated ePTFE grafts.Clinical RelevanceRapamycin-eluting ePTFE grafts decrease neointimal hyperplasia in a porcine model. Further studies are needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE grafts may allow the use of prosthetic grafts in situations in which autologous vein is unavailable and in which neointimal hyperplasia is pronounced, such as in small-diameter (

We summarise the initial results from an analysis of a 320 ks observation of the Seyfert 1 galaxy MCG–6-30-15 with the Reflection Grating Spectrometer on-board XMM-Newton .

We summarise the primary results from a 320 ks observation of the bright Seyfert 1 galaxy MCG-6-30-15 with XMM-Newton and Beppo-SAX.

The medial nucleus of the amygdala (MeA), a sexually dimorphic area, contains estrogen and androgen receptors and has an integrative role in behavioral, vegetative and endocrine activities of rats. The density of dendritic spines along the first 40 microm of dendritic length was studied in neurons from the anterodorsal (MeAD), posterodorsal (MePD) and posteroventral (MePV) aspects of the MeA in males, in virgin females during the four phases of the estrous cycle and in multiparous females in diestrus. The single-section Golgi method was employed (N=48 observations per experimental group). In the three MeA subnuclei males showed more dendritic spines than virgin females (P0.001), with the only exception being the MePD data of females in diestrus (P0.05). In virgin females, whereas more dendritic spines were found in diestrus, a decline in these values was found during the proestrus, estrus and metaestrus in the MePD and MePV (P0.05) but not in the MeAD (P0.05). Compared with virgin females in diestrus, postpartum rats showed more spines in the MeAD (P0.001) and fewer in the MePD (P0.001) but no difference was found in the MePV (P0.05). These data suggest that there are subregion-specific differences in the density of dendritic spines within the MeA and that they appear to be affected by sex, cyclic fluctuations in the levels of ovarian steroids and following pregnancy in rats. These findings may add to the understanding of the MeA neuronal plastic changes that affect the ongoing processing of sensory information and the organization of the neuroendocrine and behavioral basis of reproduction.

We present the results of a ∼200 ks deep look at the powerful distant radio galaxy 3C294 with the Chandra X-ray telescope.

Remembering Dr. Robert M. Zollinger are Dr. Larry C. Carey, professor of surgery at the University of South Florida, in Tampa, Florida; Dr. Dan W. Elliott, professor emeritus of surgery at Wright State University, in Dayton, Ohio; Dr. E. Christopher Ellison, the Robert M. Zollinger professor and chairman of surgery at Ohio State University, in Columbus, Ohio; Dr. Timothy C. Fabian, professor and chairman of surgery at the University of Tennessee, in Memphis, Tennessee; and Mrs. Letitia Roberts, the widow of Dr. Stuart S. Roberts, the first recipient of the Zollinger Chair of Surgery at Ohio State, of Peoria, Illinois.

Background: Mandatory celiotomy has been proposed for all patients with unexplained free fluid on abdominal computed tomography (CT) scanning after blunt abdominal injury. This recommendation has been based upon retrospective data and concerns over the potential morbidity from the late diagnosis of blunt intestinal injury. This study examined the rate of intestinal injury in patients with free fluid on abdominal CT after blunt abdominal trauma. Methods: This study was a multicenter prospective series of all patients with blunt abdominal trauma admitted to four level I trauma centers over 22 months. Data were collected concurrently at the time of patient enrollment and included demographics, injury severity score, findings on CT scan, and presence or absence of blunt intestinal injury. This database was specifically queried for those patients who had free fluid without solid organ injury. Results: In all, 2,299 patients were evaluated. Free fluid was present in 265. Of these, 90 patients had isolated free fluid with only 7 having a blunt intestinal injury. Conversely, 91% of patients with free fluid did not. All patients with free fluid were observed for a mean of 8 days (95% confidence interval 6.1 to 10.4, range 1 to 131). There were no missed injuries. Conclusions: Free fluid on abdominal CT scan does not mandate celiotomy. Serial observation with the possible use of other adjunctive tests is recommended.

Background: The adequacy of intermittent and continuous infusion ceftazidime for the treatment of nosocomial pneumonia in critically ill trauma patients was assessed by analyzing ceftazidime pharmacokinetics in relation to the minimum inhibitory concentration (MIC) and treatment outcome. Methods: Serial blood samples were obtained during ceftazidime therapy in 31 trauma patients. Ceftazidime pharmacokinetics were compared with that of previously studied healthy volunteers. Ceftazidime pharmacokinetics were analyzed according to the time above the MIC and treatment outcome. Results: Critically ill trauma patients had a significantly increased volume of distribution and clearance (0.32 ± 0.14 L/kg and 2.35 ± 0.89 mL · min −1 · kg −1 , respectively) compared with healthy volunteers (0.21 ± 0.03 and 1.58 ± 0.23 mL · min −1 · kg −1 ). The time above the MIC was ≥92% of the dosing interval for all patients and treatment outcomes were similar between the two treatment groups. Conclusions: Ceftazidime pharmacokinetics are significantly altered in critically ill trauma patients. Both intermittent and continuous ceftazidime regimens were equally effective for the treatment of nosocomial pneumonia caused by less virulent bacteria.

Empiri c therapy of ventilator-associated pneumonia (VAP) in surgical patients should be based on intensive care unit (ICU)–specific surveillance data, because microbial flora patterns vary widely between geographic regions as well as within hospitals. Surgical ICUs have higher VAP rates than other units. Data from the National Nosocomial Infection Surveillance (NNIS) System report Pseudomonas aeruginosa and Staphylococcus aureus to be the most frequent isolates (each 17.4%). Data from the NNIS documents high resistance patterns in ICUs compared with hospitals at large, as well as unit-specific patterns. VAP risk factors for surgical patients include thoracoabdominal surgery, altered level of consciousness, advanced age, diabetes mellitus, malnutrition, chronic obstructive pulmonary disease, and prior antibiotic administration. Promising prevention strategies include restricting ventilator circuit changes, in-line heat moisture exchange filters, semi-recumbant positioning, and continuous subglottic aspiration. Pharmacodynamics should be considered when choosing antibiotic regimens. Postantibiotic effect and time-dependent versus concentration-dependent killing should be studied in clinical trials. Current guidelines for choosing regimens have been well developed by the American Thoracic Society.

ASCA X-ray spectra of many Seyfert galaxies show a broad, skew, iron emission line consistent with emission from a relativistic disk around a black hole. The line is an important diagnostic with which to study the geometry and other properties of the accretion flow very close to the central black hole. It indicates the presence of a standard thin accretion disk within the inner few tens of gravitational radii in those objects. The general properties and observational results on the line are reviewed, together with details from two long observations of MCG-6-30-15.

We use ROSAT/ASCA X-ray spectra of high-redshift AGNs to study the intergalactic medium in the deep Universe. Because the primordial gas is likely completely ionized but not the intergalactic metals, some soft X-ray absorption features are therefore expected to be detected in the spectra of distant AGNs. We have calculated the ionization state of a metal-rich IGM, and applied the model to the joint ASCA-ROSAT X-ray spectral analysis of four AGNs at redshifts ranging from 1.8 and up to nearly 5. This test provides a constraint on the temperature and density of the IGM, which gives a well consistent picture of the physical properties of the IGM, in comparison with the results obtained from the traditional Gunn-Peterson test, and constraints given by both the cosmic microwave background and the X-ray background.

Background: We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum. Methods: Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35% hemorrhage (trauma). After 1 hour they were resuscitated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solution vehicle (n = 9). The animals were observed for 72 hours. Results: After trauma, saline solution treatment increased PMN infiltration into the peritoneum within 2 hours ( P = .035), increased peritoneal PMN elastase production (ie, cytotoxicity) by 24 hours ( P = .004), and decreased adherence of peritoneal PMNs to an artificial substrate from 4 to 72 hrs ( P = .043). The mean autopsy score was 7.0 ± 0.5. With G-CSF treatment peritoneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytotoxicity was augmented and delayed (maximum 48 hours, P = .004). Despite these changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMN-mediated damage in the lung as judged by bronchoalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myeloperoxidase, or histologic changes. The mean autopsy score was improved to 4.1 ± 0.3 ( P Conclusions: G-CSF in resuscitation fluids improved localization of an intra-abdominal septic focus by increased production of circulating PMNs, increased PMN extravasation into the peritoneal cavity, and increased PMN cytotoxicity at the abdominal septic focus, without exaggerating PMN-dependent reperfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in the multiply injured trauma patient. (Surgery 1999;126:305-13.)

The growing evidence for supermassive black holes in the centres of nearby galaxies has brought into sharper focus the question of why elliptical galaxies, rich in hot gas, do not possess quasar-like luminosities. Recent studies suggest that the presence of advection-dominated accretion flows (ADAFs) with their associated low radiative efficiency, might provide a promising explanation for the observed quiescence of these systems. Here, we present new high-frequency radio observations of the three giant, low-luminosity elliptical galaxies NGC 4649, NGC 4472 and NGC 4636 obtained using the Very Large Array (VLA) and the sub-millimetre common-user bolometer array (SCUBA) on the James Clerk Maxwell Telescope (JCMT). The new radio limits disagree severely with the canonical ADAF predictions which significantly overestimate the observed flux. If the accretion in these objects occurs in an advection-dominated mode then our radio limits imply that the emission from their central regions must be suppressed. We present the possibility that the magnetic field in the flow is extremely low or that synchrotron emission is free-free absorbed by cold material in the accretion flow. We also discuss whether slow non-radiating accretion flows may drive winds/outflows to remove energy, angular momentum and mass so that the central densities, pressures and emissivities are much smaller than in a standard ADAF (Di Matteo et al. 1998).

We report the detection of a 5.8 × 104 s (∼ 16 hr) periodicity in the 0.5–10 keV X-ray light curve of the Seyfert galaxy IRAS18325-5926, obtained from a 5-day ASCA observation. Nearly 9 cycles of the periodic variation are seen; it shows no strong energy dependence and has an amplitude of about 15 per cent. Unlike most other well-studied Seyfert galaxies, there is no evidence for strong power-law red noise in the X-ray power spectrum of IRAS18325-5926. Scaling from the QPOs found in Galactic black hole candidates suggests that the mass of the black hole in IRAS18325-5926 is ∼ 107 M⊙.

We report on a 50 ks observation of the bright Seyfert 1 galaxy MCG-6-30-15 with the Rossi X-ray Timing Explorer . The data clearly show the broad fluorescent iron line (equivalent width ∼ 242 eV for the scenario in which the primary X-ray source is above the accretion disk subtending an angle of 2π sr), and the Compton reflection continuum at higher energies. Upper limit constraints on the abundance versus reflective fraction relationship can already be placed at the 68 per cent confidence level.

First results are reported from a program for measuring the field-to-field fluctuation level of the cosmic diffuse background by using differences between the two background positions of each deep exposure with the High Energy X-ray Timing Experiment (HEXTE) instrument on the Remote X Ray Timing Explorer (RXTE). With 8 million live seconds accumulated to date a fluctuation level on the 15-25 keV band is observed which is consistent with extrapolations from the High Energy Astrophysical Observatory-1 (HEAO-1) measurements. Positive results are expected eventually at higher energies. Models of (active galactic nuclei) AGN origin will eventually be constrained by this program.

Background: The goals were (1) to characterize physiologic changes after a combined insult of hemorrhage plus sepsis in a large animal model and (2) to determine whether transient inhibition of the neutrophil CD18 adherence receptor during fluid resuscitation impairs host defense during recovery from this injury. Methods: Two series of experiments were performed in anesthetized swine. In the first series (n = 22), the cecum was ligated and incised immediately before 35% hemorrhage. After 1 hour, shed blood plus supplemental fluid was administered to restore and stabilize hemodynamics. On the basis of these results, a second series examined effects of anti-CD18 (2 mg/kg R15.7; n = 9) or its saline placebo (n = 10) administered during fluid resuscitation. Results: In the first series the mortality rate was 41% (9 of 22). Early deaths occurred 3.0 ± 0.8 days after injury and were distinguished by significantly lower neutrophil counts on resuscitation. Those alive at 7 days had intraabdominal abscesses and bacteremia. Alveoli and peribronchial spaces were congested, with edema and fibrin deposition in capillaries and alveoli. Livers were congested with biliary stasis. Despite these pathologic findings, hemodynamic, electrolyte, and serum enzyme changes were minimal. In the second series the mortality rate at 4 days was 30% with placebo (3 of 10) versus 33% with anti-CD18 (3 of 9). Lung changes (i.e., pneumonia, pleuritis, thrombosis, and edema) were similar in both groups, but liver congestion and hemorrhage were attenuated by anti-CD18. Some aspects of host defense were altered by anti-CD18. At 24 and 48 hours the oxidative burst potential for circulating granulocytes was 208% ± 57% and 383% ± 73% with placebo versus 1273% ± 351% and 762% ± 226% in anti-CD18. At 72 hours the granularity of circulating neutrophils was unchanged from baseline with placebo but was reduced to 82% ± 5% by anti-CD18. At 48 hours lipopolysaccharide-evoked tumor necrosis factor production in vitro was reduced to 62% ± 22% with placebo but was increased to 148% ± 16% with anti-CD18. Conclusions: Anti-CD18 during fluid resuscitation did not increase vulnerability to endogenous pathogens because the transient inhibition of neutrophil demargination was balanced by enhanced oxidative burst, degranulation, and production of tumor necrosis factor in circulating cells later during recovery. Thus a single administration of antiadhesion therapy does not worsen posttrauma outcome even if given during ongoing sepsis. (Surgery 1998;123:679-91.)

Background. The purpose of this experimental study was to test whether transfusion potentiated physiologic changes associated with fluid resuscitated trauma in controlled conditions. Methods. Anesthetized and ventilated mongrel pigs were subjected to soft-tissue injury plus 35% hemorrhage and 1 hour shock and then were resuscitated with either autologous (shed) or heterologous (crosstransfused) fresh whole blood. Leukocyte differential counts, T-lymphocyte subsets, neutrophil adherence molecule (CD18) expression, granulocyte oxidative burst, plasma cortisol, and serum chemistries were monitored in awake animals with indwelling catheters on 3 consecutive days. Changes were referenced to preinjury baseline values and to a control group that received heterologous transfusion but no shock. To determine whether these changes might have influenced host defense, a low-dose challenge with Escherichia coli endotoxin (lipopolysaccharide [LPS]; 1 to 2 μg/kgfor 30 minutes) was administered on day 4. Results. During recovery, neutrophil counts, neutrophil CD18 expression, and granulocyte oxidative burst were generally increased, but the changes were not potentiated by transfusion. Lymphocyte subpopulations remained relatively constant. Serum enzyme markers were elevated with trauma plus shed blood or trauma plus cross-transfusion, but they remained essentially unchanged after heterologous transfusion only. Plasma cortisol, a nonspecific index of stress, peaked at 3 to 6 times higher than baseline. The increases tended to be higher and later with heterologous transfusion only, relative to trauma plus shed blood or trauma plus cross-transfusion. The delayed LPS challenge evoked profound but transient pulmonary hypertension and leukopenia, followed by subsequent hypoxemia; the time courses and magnitude of these changes were similar in all groups. Conclusions. If these measured variables before and after LPS challenge are a valid index of host defense in this species, then a 35% transfusion does not potentiate the risk for posttrauma immune dysfunction when the magnitude of injury is constant. Thus the predisposition to infection after human trauma might be due to cold storage of blood, separation of blood into components, or other transfusion-related practices rather than to transfusion per se.

Background. Individual trials of small-volume resuscitation of 7.5% NaCl (HS) with and without 6% dextran 70 (HSD) for the treatment of trauma have failed to provide convincing evidence of efficacy. We performed a meta-analysis to evaluate the effects of HS and HSD on survival until discharge or for 30 days. We identified eight double-blinded, randomized controlled trials of HSD and six trials of HS. In all cases, administration of 250 ml of HSD or HS was compared with a control group administration of 250 ml of isotonic crystalloid for the treatment of hypotension either in the field or at admission to the emergency department. Methods. A fixed-effects meta-analysis was performed with the Mantel-Haenszel method of combining results from multiple studies. Results. Overall, HS was not effective in improving survival with a weighted mean difference in survival of the HS group versus the isotonic control group equal to 0.6%. The results with HSD were more positive, with an increase in survival in seven of eight trials. The mean difference in survival rates favoring HSD (n = 615) over controls (n = 618) was 3.5% (p = 0.14, two-tailed; p = 0.07, one-tailed). The odds ratio was estimated to be 1.20 in favor of HSD with a 95% confidence interval of 0.94 to 1.57. Conclusions. The meta-analysis of the available data shows that HS is not different from the standard of care and that HSD may be superior.

We have shown that therapy directed at polymorphonuclear neutrophil (PMN) CD18 receptors attenuates sequelae associated with a post-trauma endotoxin (lipopolysaccharide [LPS]) challenge. Platelet activating factor (PAF) stimulates PMNs by CD18-independent pathways, and WEB-2086, a PAF receptor antagonist, blunts septic symptoms in many experimental models. This study tested the hypothesis that the blockade of non-CD18 dependent PMN adherence attenuates trauma- and LPS-evoked pulmonary dysfunction.We performed three experiments. First, anesthetized swine were subjected to hind-limb trauma and 30% hemorrhage. After 1 hour animals were resuscitated with shed blood, lactated Ringer's solution (LRS), and WEB-2086 (10 mg/kg/hr) or vehicle. After a 72-hour recovery period, LPS was administered. LPS was then administered without an earlier episode of traumatic shock to animals treated with WEB-2086 or vehicle. Finally, PAF was infused before and after trauma and a dose response curve was obtained.Surprisingly, PAF blockade increased mortality after trauma (5 of 11 WEB-2086 animals versus 1 of 9 vehicle animals; p = 0.15) and depressed cardiac index and O2 delivery at 72 hours (p0.05). After LPS administration WEB-2086 treated pigs were unable to manifest the hyperdynamic circulatory compensation seen in the vehicle pigs. In the absence of traumatic shock, WEB-2086 was associated with reduced mortality (four of five WEB-2086 treated pigs versus two of five vehicle pigs survived 5 hours; p = 0.07) and improved arterial PO2 (p = 0.05) and base excess (p = 0.04) 60 minutes after LPS administration. The dose response curve for PAF infusion on the cardiac index was altered after trauma compared with the nontraumatized state.Because WEB-2086 had unexpected and fundamentally opposite properties before and after trauma, PAF may have a previously undescribed homeostatic role in the compensatory response to injury. These results also suggest that blockade of endogenous inflammatory mediators can have a positive or negative action, depending on the timing of administration and the preexisting condition.

Summary Background Some studies have suggested that a lowprotein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF. Methods A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2–18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation-ie, 0·8–1·1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study. Findings The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group −9·7 [SD 8·0] vs −10·7 [11·8] mL/min per 1·73m 2 ; non-progressive group −2·5 [7·5] vs −4·3 [10·0] mL/min per 1·73 m 2 ). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R 2 =0·259) and systolic blood pressure (partial R 2 =0·087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year. Interpretation A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.

X-ray absorption measurements directly probe the torus in Seyfert 2 galaxies and X-ray reflection studies can reveal that part of the torus which is Thomson-thick in Seyfert 1 galaxies. Current observations of Seyfert 1 however show no evidence for this last component, indicating that the Thomson-thick part of a typical torus covers less than about 30% of the Sky as seen from the central source. ASCA data on more powerful distant objects shows that the torus in the type 2 quasar IRAS P09104 covers about 20% of the Sky and in 2 PG quasars at z ∼ 1 it covers less than about a quarter of the Sky. ROSAT data on radio galaxies helps define the absorption there, indicating that the torus in distant FRII sources exceeds 1023 cm−2. The X-ray Background requires that most of the primary power in AGN is absorbed, thereby giving a dominant role to the torus.

Few guidelines are available with which to facilitate treatment in patients with noniatrogenic injuries of the esophagus. Early diagnosis and proper management are essential if a good outcome is to be expected. In an effort to define better the treatment of patients with penetrating and blunt injuries of the esophagus, we report our recent 5-year experience at an urban trauma center. From July 1988 to June 1993, nineteen patients with esophageal perforations from penetrating (18) and blunt (1) trauma were identified by our trauma registry. There was no mortality in this group of patients and morbidity was mostly due to associated injuries. Eleven cervical esophageal injuries were repaired. One cervical injury was treated by stopping oral intake and giving intravenous antibiotics. The neck was not drained in 10 of the surgical cases. In 1 patient a tracheoesophageal fistula developed, which later was repaired with a pectoralis muscle flap. Seven perforations were identified in the thoracic (2) and abdominal (5) portions of the esophagus. All were due to gunshot wounds. In 4 cases, a fundal wrap was used to reinforce the repairs. Postoperative contrast studies confirmed that all repairs were intact. We conclude that penetrating and blunt tears of the esophagus can be repaired safely with minimal mortality. Morbidity is usually from associated injuries such as to the spinal cord and trachea. When identified early, cervical esophageal injuries do not need to be drained routinely.

Catalogues of several types of extragalactic objects have been cross-correlated with Ginga measurements of the X-ray background intensity. Some of these catalogues give rise to significant signals, meaning that either sources in them or some other sources clustered around them produce a fraction of the X-ray background. The significance of these results has been established using bootstrap and X-ray background simulations. An expression to infer the local X-ray emissivity from the cross-correlation signal is given and applied to two galaxy catalogues (UGC and IRAS) for which the signal is more significant (>95 per cent). Values of ∼ 1039h ergs−1 Mpc−3 are obtained, implying that ≤ 30 per cent of the X-ray background could be produced by a non-evolving population of galaxies.

In an attempt to prevent paraplegia, a devastating complication common after the repair of traumatic rupture of the aorta, we have used partial cardiopulmonary bypass. Most of the patients in our series (79.5%) underwent other major surgical procedures immediately before or after the aortic repair. Eight of the 110 patients died before aortic repair could be performed. The aorta was not repaired in 3, because of other injuries. In 9, the repair was done without a shunt or bypass; 4 patients died and 2 (22.2%) survived without paraplegia. One of the 2 who underwent repair with a Gott shunt died; the survivor suffered no cord damage. Of the 88 patients whose repair was carried out under cardiopulmonary bypass, 6 died and 80 (90.9%) survived without paraplegia. None of the last 39 patients has become paraplegic, as vasodilator treatment is now discontinued during the cross-clamp period. Serious intracranial injury was present in 19 patients; in 3 (15.8%) the injury became worse after repair. There was no evidence of new or increased intraabdominal bleeding during heparinization. Except in the event of pulmonary lacerations, systemic heparin therapy was not associated with major problems.

Background. Histamine H 2 antagonists (e.g., ranitidine) are generally thought to specifically reduce gastric acid secretion and are commonly used for stress ulcer prophylaxis in critically ill patients because of their efficacy and safety profile. A few reports suggest that ranitidine might also bind to extragastric sites and/or act as an immunomodulator. The potential effects on posttraumatic sepsis are unknoum. Methods. Mongrel pigs (n=24) were anesthetized with fentanyl, injured by a 10 kg steel bar dropped from a height of 1 m onto the fleshy portion of the posterior thigh, and then 35% of their blood volume was drained through the arterial catheter. All the shed blood plus two times the hemorrhage volume as lactated Ringer's solution was infused after a 1-hour shock period. Either vehicle or ranitidine (1.5 mg/kg) was intravenously administered at the time of resuscitation and every 12 hours thereafter in a blinded fashion. After 72 hours a septic challenge was administered (15 μg/kg Escherichia coli lipopolysaccharide [LPS]×30 min). Serial gastroscopy, gastric pH, hemodynamics leukocyte counts, cortisol, and tumor necrosis factor were recorded for 180 minutes after LPS. Results. Immediately before LPS all hemodynamic variables were identical between treatments, but gastric pH was slightly higher and stress gastritis was marginally lower with ranitidine. LPS caused profound leukopenia and a hyperdynamic circulatory response (i.e., tachycardia, increased cardiac output, and decreased peripheral vascular resistance at relatively constant blood pressure); these changes were not altered by ranitidine. Gastric pH remained elevated after LPS with ranitidine, but LPS-induced gastritis was not modified. Ranitidine delayed the LPS-induced ventilation-perfusion imbalance and attenuated the peak increase in the proinflammatory cytokine, tumor necrosis factor, without altering its antiinflammatory opponent, cortisol. Similar changes were observed in four additional animals treated with cimetidine. The proportion of circulating neutrophils and lymphocytes was slightly altered 180 minutes after LPS, but there was no obvious effect on T lymphocytes in vivo, and no effect on the LPS-induced increase in neutrophil CD18 expression in vitro was seen. Conclusions. (1) Ranitidine increased gastric pH, which blunted the stress gastritis caused by trauma but not that caused by LPS; (2) ranitidine delayed the early LPS-evoked pulmonary changes and reduced the tumor necrosis factor spike, which is consistent with a favorable immunomodulatory action that has been reported in patients who are critically ill or are undergoing an elective abdominal surgical procedure; (3) the mechanism is probably related to H 2 receptor antagonism rather than to a nonspecific side effect of ranitidine, which suggests that histamine may have a previously unrecognized role in posttraumatic septic responses; and (4) the site of action is probably not in the heart or peripheral resistance vessels, but salutary effects on circulating lymphocytes or neutrophils cannot be excluded.

Hepatic artery pseudoaneurysm (HPA) with hemobilia is an unusual complication of hepatic trauma. Initial operative management can have an impact on the development of HPA, and definitive management is difficult. A total of 482 consecutive patients with liver injury were prospectively analyzed. Six of these (1.2%) developed HPA with hemobilia. Three patients developed HPA after penetrating injuries, and 3 after blunt trauma. All 6 patients had hemobilia with massive upper gastrointestinal hemorrhage; HPA was confirmed by angiography. A total of 80% had bile leaks as revealed by hepatobiliary scans. One patient was nonseptic and had a small intrahepatic cavity, and the patient underwent successful embolization of the HPA. The remaining 5 had unexplained sepsis with large intrahepatic cavities and underwent operation. Two died due to massive blood loss and coagulopathy during attempted cavity débridement prior to gaining vascular control. One had right hepatic artery ligation in lieu of resection and subsequent lobectomy after recurrence of hemobilia; the other 2 had formal hepatic resections. No survivors had further rebleeding. We conclude that (1) HPA with hemobilia is predisposed by bile leak; (2) embolization appears appropriate for patients with small cavities without sepsis; and (3) débridement and drainage, which may require formal resection, are necessary for those with large cavities and/or sepsis after vascular control is obtained either by preoperative embolization or intraoperatively.

There were 73 evaluable patients entered into a prospective, double-blinded trial comparing aztreonam/clindamycin (A/C) to gentamicin/clindamycin (G/C) for the prevention of infection after penetrating abdominal trauma. Aztreonam was administered at a dosage of 2 g every 8 hours and gentamicin at 5 mg/kg for the first 24 hours and then adjusted by serum monitoring to a peak of 6 to 8 micrograms/mL and a trough of less than 2 micrograms/mL; all patients received 900 mg of clindamycin every 8 hours. Patients with colon wounds received 4 days of antibiotics, and the remaining patients received a 24-hour course. Gunshot wounds occurred in 69% of patients: 74% of all patients had some hollow viscus injury, and 26% had only solid viscus injury. The groups were well matched according to abdominal trauma index, percentage with colon injury, and transfusion requirements. Failures occurred in eight patients (11%): two wound infections, five intra-abdominal infections, and one case of necrotizing fasciitis. Seven infections occurred in 36 (19%) G/C patients compared with 1 in 37 (3%) A/C patients (p0.03). The hospital stay was 12 +/- 11 days for G/C patients and 8 +/- 7 for A/C patients (p0.12). The superiority of the A/C regimen may be partially attributable to relative underdosing of gentamicin (approximately half of the patients had inadequate levels after 24 hours) combined with a favorable pharmacokinetic profile (significantly prolonged half-life) of aztreonam in this clinical setting.

Compared with total parenteral nutrition, enteral feeding via jejunostomy reduces septic complications in patients with severe trauma. However, violation of the bowel with insertion of a jejunostomy tube may increase the risk of intra-abdominal abscess (IAA), particularly if no simultaneous gastrointestinal tract injury exists. The records of 123 patients requiring splenectomy for trauma at a level I trauma center during a 6-year period (1986 to 1992) were reviewed to examine the incidence of IAA in patients with and without simultaneous jejunostomy placement in the presence and absence of gastrointestinal tract injuries. Thirty patients had jejunostomies placed (J), and 93 did not (NoJ). There were no significant differences between the groups in age, Abdominal Trauma Index, Injury Severity Score, or transfusion requirements. The incidence of IAA was not significantly different between the J and NoJ groups in the presence or absence of gastrointestinal tract injuries. Thus, jejunostomy placement does not increase the incidence of IAA after splenectomy regardless of the presence of a gastrointestinal tract injury.

Acute cardiac failure, pulmonary edema, and ischemia of the brain, cord, and other structures pose special problems with trauma to the aortic arch and its branches. Data on 93 such cases are reported. Diagnosis was made by clinical examination in hemodynamically unstable patients and led to immediate operation in 61.3%. Patients in stable condition had angiography, which localized the injury and allowed planning of incision and bypass shunts. In left subclavian artery injuries, anterior thoracotomy was best for proximal control regardless of wound entry sites; midline sternotomy with sternocleidomastoid extension was usually adequate for other vessels. Flow was reestablished in all carotid injuries; there were no neurological complications. Temporary or permanent bypass shunts during periods of proximal aortic occlusion were valuable in decreasing cardiac afterload, maintaining circulation to the brain, and allowing an unhurried methodical approach to the hematoma. Occlusion of one or more venae cavae alleviated acute cardiac dilatation during brief periods of ascending aortic clamping. Associated trauma contributed to the high mortality.

Study Objective: To examine and compare the mechanism of injury, diagnostic findings, initial methods of airway management, and outcome of patients who had upper airway injuries. Design: A retrospective review of hospital records. Setting: A large metropolitan, university-affiliated trauma center. Patients: Forty-six cases of upper airway injuries admitted between 1984 and 1988. Interventions: Diagnostic methods included clinical examination, cervical and thoracic radiographs, bronchoscopy and computerized tomographic (CT) scan. Therapeutic interventions ranged from conservative management with or without endotracheal intubation to operative reconstruction. Measurements and Main Results: Mechanism of injury was knife stab wound in 9 cases, gunshot wound in 17 cases, and blunt trauma in 20 cases. Location was the larynx in 13 cases, trachea in 24 cases, cricoid cartilage in 5 cases, and multiple sites in 4 cases. Diagnostic findings varied considerably according to the mechanism of injury, but radiographic evidence of soft tissue air and wounds opening into the airway were common findings. CT scan and bronchoscopy also were useful diagnostic tools. Overall mortality was 24%, which did not vary according to patient age or mechanism of injury. The airway injury itself was a primary or contributory cause of death in four cases, two of which were tracheal injuries and two injuries at the cricotracheal junction. Conclusions: In any patient with possible upper airway injury, plain radiographs of the chest and neck should be obtained to aid in the diagnosis. Elective intubation should be attempted only with a surgical team present and prepared for emergency tracheotomy. Fiber-optic bronchoscopy could be a valuable aid for both intubation and evaluation in such cases.

The use of fluctuation analyses of the extragalactic X-ray Background to determine source counts down to very faint levels is reivewed. It is shown that the instrumentation being developed for ASTRO D (expected to be launched in 1993) will be able to resolve a high percentage of the background (via analysis of fluctuations) and that its spectral coverage will also give an answer to the mismatch of source counts in different energy bands. Estimates of the required exposure times are given.

A recent retrospective study proposed that the following screening criteria be used in identifying critically ill trauma patients receiving aminoglycosides who are at significant risk to develop renal dysfunction: (1) post-admission shock, (2) minimum serum concentration more than 2 mg/L, and (3) diagnosis of septicemia. The major purpose of the present study was to validate these criteria and design a corresponding algorithm for clinical use. All patients admitted to a trauma intensive care unit and receiving an aminoglycosides was also studied. All patients studied over a 7-month period. A control group not receiving aminoglycosides was also studied. All patients were evaluated for the presence of renal dysfunction (i.e., serum creatinine increase greater than or equal to 0.5 mg/dL). Univariate and multivariate statistical analyses were used to compare potential associated risk factors. The overall renal dysfunction incidence was 10% in the treatment patients (n = 93) versus 5% in the control patients (n = 199) (p = 0.13). Sensitivity and specificity of the screening criteria were 67% and 92%, respectively. The predictive values of a positive and negative test relative to correctly labeling patients at high risk or low risk to develop renal dysfunction were 46% and 96%, respectively. Major risk factors associated with renal dysfunction in the treatment group were post-admission shock, minimum serum concentration more than 2 mg/L, and liver dysfunction. Use of three major risk factors has excellent predictive value in identifying severely traumatized patients at low risk for developing renal dysfunction while receiving aminoglycosides. The modest predictive value of a positive test results in conservative management of patients by avoidance of aminoglycosides, i.e., use of alternative antimicrobial agents.

Observations and interpretations of the X- and γ-ray continuum of active galactic nuclei (AGN) are discussed. Special emphasis is made of the possibility that electron-positron pairs are produced which process much of the power in the source. This would affect both the spectrum and time variability of the source, and provide an intuitive explanation of the high energy break seen in AGN.

Properties of the iron line in Cen X-3 have been studied, using the gas scintillation proportional counter onboard EXOSAT. The iron line energy is seen to be constant (kT = 6.59 ± 0.06 keV) over orbital and pulse periods. On the other hand the iron line intensity is seen to vary with both periods. The pulse period variations are sinusoidal, but the orbital period variations are more complex. These variations can be explained assuming that the iron line emission comes from, at least, two different emitting regions; the Alfven sphere and the primary's atmosphere. The pulse period variations are produced at the Alfven sphere and the orbital period variations at the primary's atmosphere.