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Introduction: Warfighters are issued hard body armor designed to defeat ballistic projectiles. The resulting backface deformation can injure different thoracoabdominal organs. Developed over decades ago, the behind armor blunt impact criterion of maximum 44 mm depth in clay continues to be used independent of armor type or impact location on the thoracoabdominal region covered by the armor. Because thoracoabdominal components have different energy absorption capabilities, their mode of failures and mechanical properties are different. These considerations underscore the lack of effectiveness of using the single standard to cover all thoracoabdominal components to represent the same level of injury risk. The objective of this pilot study is to conduct cardiac impact tests with a live animal model and analyze biomechanical injury candidate metrics for behind armor blunt trauma applications., Materials and Methods: Live swine tests were conducted after obtaining approvals from the U.S. DoD. Trachea tubes. An intravenous line were introduced into the swine before administering anesthesia. Pressure transducers were inserted into lungs and aorta. An indenter simulating backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers delivered impact to the heart region. The approved test protocol included 6-hour monitoring and necropsies. Indenter accelerometer signals were processed to compute the velocity and deflection, and their peak magnitudes were obtained. The deflection-time signal was normalized with respect to chest depth along the impact axis. The peak magnitude of the viscous criterion, kinetic energy, force, momentum and stiffness were obtained., Results: Out of the 8 specimens, 2 were sham controls. The mean total body mass and soft tissue thickness at the impact site were 81.1 ± 4.1 kg and 3.8 ± 1.1 cm. The peak velocities ranged from 30 to 59 m/s, normalized deflections ranged from 15 to 21%, and energies ranged from 105 to 407 J. The range in momentum and stiffness were 7.0 to 13.9 kg-m/s and 22.3 to 79.9 N/m. The maximum forces and impulse data ranged from 2.9 to 11.7 kN and 1.9 to 5.8 N-s. The peak viscous criterion ranged from 2.0 to 5.3 m/s. One animal did not sustain any injuries, 2 had cardiac injuries, and others had lung and skeletal injuries., Conclusions: The present study applied blunt impact loads to the live swine cardiac region and determined potential candidate injury metrics for characterization. The sample size of 6 swine produced injuries ranging from none to pure skeletal to pure organ trauma. The viscous criterion metric associated with the response of the animal demonstrated a differing pattern than other variables with increasing velocity. These findings demonstrate that our live animal experimental design can be effectively used with testing additional samples to develop behind armor blunt injury criteria for cardiac trauma in the form of risk curves. Injury criteria obtained for cardiac trauma can be used to enhance the effectiveness of the body armor, reduce morbidity and mortality, and improve warfighter readiness in combat operations., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current behind armor blunt trauma standard. The purpose of this study was to report on the methods, procedures, and data collected from swine., Materials and Methods: Live swine tests were conducted after obtaining approvals from the local institution and the Army Care and Use Review Office of the U.S. Department of Defense. Trachea tubes and an intravenous line were introduced before administering anesthesia. Pressure transducers were inserted into the lungs and aorta. An indenter simulating the backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers was used to deliver impact loading to the liver region. A triaxial accelerometer was included in the indenter design. The animals were monitored for 6 hours, necropsies were performed, and injuries were identified. Biomechanical data of the energy, velocity, deflection, viscous criterion, force, and impulse variables were obtained for each test., Results: Peak accelerations, velocities, deflections, forces, impulse, and energies ranged from 897 to 5,808 g, 21 to 59 m/s, 1.96 to 8.87 cm, 2.3 to 13.1 kN, 1.1 to 7.1 Ns, and 58 to 387 J, respectively. The peak viscous criterion ranged from 0.8 to 5.8 m/s. All animals survived the 6-hour survival period. Three animals responded with liver lacerations while the remaining 4 did not have any injuries., Conclusion: The experimental design based on parallel tests with whole body human cadavers and cadaver swine was found to be successful in delivering controlled impacts to the liver region of live swine and reproducing liver injuries. Previously used biomechanical measures as potential candidates for injury criteria development were obtained. Using this proven model, tests with additional samples are needed to develop injury risk curves for liver impacts and obtain regional (liver) injury criteria., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The current behind armor blunt trauma (BABT) injury criterion uses a single penetration limit of 44 mm in Roma Plastilina clay and is not specific to thoracoabdominal regions. However, different regions in the human body have different injury tolerances. This manuscript presents a matched-pair hybrid test paradigm with different experimental models and candidate metrics to develop regional human injury criteria., Methods: Live and cadaver swine were used as matched pair experimental models. An impactor simulating backface deformation profiles produced by body armor from military-relevant ballistics was used to deliver BABT loading to liver and lung regions in cadaver and live swine. Impact loading was characterized using peak accelerations and energy. For live swine, physiological parameters were monitored for 6 hours, animals were euthanized, and a detailed necropsy was done to identify injuries to skeletal structures, organs and soft tissues. A similar process was used to identify injuries to the cadaver swine for targeted thoracoabdominal regions., Results: Two cadavers and one live swine were subjected to BABT impacts to the liver. One cadaver and one live swine were subjected to BABT impacts to the left lung. Injuries to both regions were similar at similar energies between the cadaver and live models., Conclusions: Swine is an established animal for thoracoabdominal impact studies in automotive standards, although at lower insult levels. Similarities in BABT responses between cadaver and live swine allow for extending testing protocols to human cadavers and for the development of scaling relationships between animal and human cadavers, acting as a hybrid protocol between species and live and cadaver models. Injury tolerances and injury risk curves from live animals can be converted to human tolerances via structural scaling using these outcomes. The present experimental paradigm can be used to develop region-based BABT injury criteria, which are not currently available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: For behind armor blunt trauma (BABT), recent prominent BABT standards for chest plate define a maximum deformation distance of 44 mm in clay. It was developed for soft body armor applications with limited animal, gelatin, and clay tests. The legacy criterion does not account for differing regional thoracoabdominal tolerances to behind armor-induced injury. This study examines the rationale and approaches used in the legacy BABT clay criterion and presents a novel paradigm to develop thoracoabdominal regional injury risk curves., Materials and Methods: A review of the original military and law enforcement studies using animals, surrogates, and body armor materials was conducted, and a reanalysis of data was performed. A multiparameter model analysis describes survival-lethality responses using impactor/projectile (mass, diameter, and impact velocity) and specimen (weight and tissue thickness) variables. Binary regression risk curves with ±95% confidence intervals (CIs) and peak deformations from simulant tests are presented., Results: Injury risk curves from 74 goat thorax tests showed that peak deflections of 44.7 mm (±95% CI: 17.6 to 55.4 mm) and 49.9 mm (±95% CI: 24.7 to 60.4 mm) were associated with the 10% and 15% probability of lethal outcomes. 20% gelatin and Roma Plastilina #1 clay were stiffer than goat. The clay was stiffer than 20% gelatin. Penetration diameters showed greater variations (on a test-by-test basis, difference 36-53%) than penetration depths (0-12%) across a range of projectiles and velocities., Conclusions: While the original authors stressed limitations and the importance of additional tests for refining the 44 mm recommendation, they were not pursued. As live swine tests are effective in developing injury criteria and the responses of different areas of the thoracoabdominal regions are different because of anatomy, structure, and function, a new set of swine and human cadaver tests are necessary to develop scaling relationships. Live swine tests are needed to develop incapacitation/lethal injury risk functions; using scaling relationships, human injury criteria can be developed., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: The decision to withdraw life sustaining treatment (WDLST) in older adults with traumatic brain injury is subject to wide variability leading to nonbeneficial interventions and unnecessary use of hospital resources. We hypothesized that patient and hospital factors are associated with WDLST and WDLST timing., Methods: All traumatic brain injury patients ≥65 with Glasgow coma scores (GCS) of 4-11 from 2018 to 2019 at level I and II centers were selected from the National Trauma Data Bank. Patients with head abbreviated injury scores 5-6 or death within 24 h were excluded. Bayesian additive regression tree analysis was performed to identify the cumulative incidence function (CIF) and the relative risks (RR) over time for withdrawal of care, discharge to hospice (DH), and death. Death alone (no WDLST or DH) served as the comparator group for all analyses. A subanalysis of the composite outcome WDLST/DH (defined as end-of-life-care), with death (no WDLST or DH) as a comparator cohort was performed., Results: We included 2126 patients, of whom 1957 (57%) underwent WDLST, 402 (19%) died, and 469 (22%) were DH. 60% of patients were male, and the mean age was 80 y. The majority of patients were injured by fall (76%, n = 1644). Patients who were DH were more often female (51% DH versus 39% WDLST), had a past medical history of dementia (45% DH versus 18% WDLST), and had lower admission injury severity score (14 DH versus 18.6 WDLST) (P < 0.001). Compared to those who DH, those who underwent WDLST had a lower GCS (9.8 versus 8.4, P < 0.001). CIF of WDSLT and DH increased with age, stabilizing by day 3. At day 3, patients ≥90 y had an increased RR of DH compared to WDLST (RR 2.5 versus 1.4). As GCS increased, CIF and RR of WDLST decreased, while CIF and RR of DH increased (RR on day 3 for GCS 12: WDLST 0.42 versus DH 1.31).Patients at nonprofit institutions were more likely to undergo WDLST (RR 1.15) compared to DH (0.68). Compared to patients of White race, patients of Black race had a lower RR of WDLST at all timepoints., Conclusions: Patient and hospital factors influence the practice of end-of-life-care (WDLST, DH, and death), highlighting the need to better understand variability to target palliative care interventions and standardize care across populations and trauma centers., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients prescribed higher opioid dosages are at increased risk of overdose and death without added pain reduction. Increases in opioid prescribing continue to fuel the epidemic. We hypothesized a comprehensive guideline to standardize opioid prescribing would decrease postdischarge dosages for patients experiencing trauma without requiring additional refills., Methods: This quasiexperimental study compared opioid prescribing by trauma providers before and after the implementation of a departmental guideline on April 1, 2019, aimed at aligning opioid prescription patterns with Centers for Disease Control and Prevention recommendations. Patients prescribed opioids before implementation were the control group, whereas patients prescribed opioids after were the intervention group. The primary outcome was the proportion of patients receiving ≥50 morphine milligram equivalents per day., Results: We identified 293 and 280 patients experiencing trauma in the control and intervention groups, respectively. There were no differences between the groups' Injury Severity Score (P = .69) or the frequency of having a procedure performed (P = .80). Total morphine milligram equivalents and maximum morphine milligram equivalents per day were 16% and 25% lower, respectively, in the intervention group compared with the control group (P < .001). The proportion of trauma patients prescribed ≥50 morphine milligram equivalents per day at discharge decreased from 57% to 18% after implementation (P < .001). The proportion of trauma patients prescribed ≥90 morphine milligram equivalents per day also decreased, from 37% to 14% (P < .001). There was no significant increase in the frequency of refill requests (P = .105) or refill prescriptions (P = .099) after discharge., Conclusion: A departmental guideline aimed at optimizing opioid prescription patterns successfully lowers the amount of morphine milligram equivalents prescribed to trauma patients and improves compliance with Centers for Disease Control and Prevention recommendations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Civilian extremity trauma with vascular injury carries a significant risk of morbidity, limb loss, and mortality. We aim to describe the trends in extremity vascular injury repair and compare outcomes between trauma and vascular surgeons., Methods: We performed a single-center retrospective review of patients 18 years or older with extremity vascular injury requiring surgical intervention between January 2009 and December 2019. Demographics, injury characteristics, operative course, and hospital course were analyzed. Descriptive statistics were used to examine management trends, and outcomes were compared for arterial repairs. Multivariate regression was used to evaluate surgeon specialty as a predictor of complications, readmission, vascular outcomes, and mortality., Results: A total of 231 patients met our inclusion criteria; 80% were male with a median age of 29 years. The femoral vessels were most commonly injured (39.4%), followed by the popliteal vessels (26.8%). Trauma surgeons performed the majority of femoral artery repairs (82%), while vascular surgeons repaired the majority of popliteal artery injuries (84%). Both had a similar share of brachial artery repairs (36% vs. 39%, respectively). There were no differences in complications, readmission, vascular outcomes, and mortality. Median time from arrival to operating room was significantly shorter for trauma surgeons. There was a significant downward trend between 2009 and 2017 in the proportion of total and femoral vascular procedures performed by trauma surgeons. On multivariate regression, surgical specialty was not a significant predictor of need for vascular reintervention, prophylactic or delayed fasciotomies, postoperative complications, or readmissions., Conclusion: Traumas surgeons arrived quicker to the operating and had no difference in short-term clinical outcomes of brachial and femoral artery repairs compared with patients treated by vascular surgeons. Over the last decade, there has been a significant decline in the number of open vascular repairs done by trauma surgeons., Level of Evidence: Therapeutic/Care Management, Level IV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nonoperative management of adhesive small bowel obstruction (SBO) is successful in up to 80% of patients. Current recommendations advocate for computed tomography (CT) scan in all patients with SBO to supplement surgical decision-making. The hypothesis of this study was that cumulative findings on CT would predict the need for operative intervention in the setting of SBO., Methods: This is an analysis of a retrospectively and prospectively collected adhesive SBO database over a 6-year period. A Bowel Ischemia Score (BIS) was developed based on the Eastern Association for the Surgery of Trauma guidelines of CT findings suggestive of bowel ischemia. One point was assigned for each of the six variables. Early operation was defined as surgery within 6 hours of CT scan., Results: Of the 275 patients in the database, 249 (90.5%) underwent CT scan. The operative rate was 28.3% with a median time from CT to operation of 21 hours (Interquartile range 5.2-59.2 hours). Most patients (166/217, 76.4%) with a BIS of 0 or 1 were successfully managed nonoperatively, whereas the majority of those with a BIS of 3 required operative intervention (5/6, 83.3%). The discrimination (area under the receiver operating characteristic curve) of BIS for early surgery, any operative intervention, and small bowel resection were 0.83, 0.72, and 0.61, respectively., Conclusion: The cumulative signs of bowel ischemia on CT scan represented by BIS, rather than the presence or absence of any one finding, correlate with the need for early operative intervention.

Introduction: Blunt pelvic fractures can be associated with major pelvic bleeding. The significance of contrast extravasation (CE) on computed tomography (CT) is debated. We sought to update our experience with CE on CT scan for the years 2009-2014 to determine the accuracy of CE in predicting the need for angioembolization., Methods: This is a retrospective review of the trauma registry and our electronic medical record from a Level I trauma center. Patients seen from July 1, 2009, to September 7, 2014, with blunt pelvic fractures and contrast-enhanced CT were included. Standard demographic, clinical, and injury data were obtained. Patient records were queried for CE, performance of angiography, and angioembolization. Positive patients were those where CE was associated with active bleeding requiring angioembolization. All other patients were considered negative., Results: There were 497 patients during the study time period with blunt pelvic fracture meeting inclusion criteria, and 75 patients (15%) had CE. Of those patients with CE, 30 patients (40%) underwent angiography, and 17 patients (23%) required angioembolization. The sensitivity, specificity, positive predictive value, and negative predictive value of CE on CT were 100%, 87.9%, 22.7%, and 100%, respectively. Two patients without CE underwent angiography but did not undergo embolization. Patients with CE had higher mortality (13 vs. 6%, p < 0.05) despite not having higher ISS scores., Conclusions: This study reinforces that CE on CT pelvis with blunt trauma is common, but many patients will not require angioembolization. The negative predictive value of 100% should be reassuring to trauma surgeons such that if a modern CT scanner is used, and there is no CE seen on CT, then the pelvis will not be a source of hemorrhagic shock. All of these findings are likely due to both increased comfort with observing CEs and the increased sensitivity of modern CT scanners., Level of Evidence: Therapeutic/care management study, level IV.

This article provides a review of commonly prescribed medications in the surgical ICU, focusing on sedatives, antipsychotics, neuromuscular blocking agents, cardiovascular agents, anticoagulants, and antibiotics. A brief overview of pharmacology is followed by practical considerations to aid prescribers in selecting the best therapy within a given category of drugs to optimize patient outcomes., (Copyright © 2012. Published by Elsevier Inc.)

Background: Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE), but physicians are cautious with chemical prophylaxis in these patients because of concern about exacerbating intracranial hemorrhage. We hypothesized that early use of chemical thromboprophylaxis would reduce VTE incidence without increasing intracranial hemorrhage., Study Design: Records of all patients admitted with a TBI to a Level I trauma center from 2006 to 2008 were reviewed. TBI was defined as intracranial hemorrhage, hematoma, contusion, or diffuse axonal injury with a head Abbreviated Injury Scale score >2. Patients were excluded if they were discharged or died within 72 hours of admission. Chemical prophylaxis was defined as subcutaneous or intravenous unfractionated heparin or low molecular weight heparin before any VTE diagnosis. Progression of TBI was defined by worsening CT findings. VTE was defined as deep venous thrombosis or pulmonary embolus confirmed by radiology reports. Primary outcomes were progression of hemorrhage and VTE events., Results: Eight hundred and twelve of the 1,258 patients admitted to the trauma center with a TBI met study criteria. Chemical thromboprophylaxis was given to 49.5% (n = 402). Mean head Abbreviated Injury Scale score was 3.4 in both groups. One hundred and sixty-nine patients started prophylaxis within 48 hours and 242 patients began within 72 hours. Patients receiving chemical prophylaxis had a lower incidence of VTE (1% versus 3%; p = 0.019). Although not statistically significant, they also had a lower rate of injury progression, 3% versus 6% (p = 0.055)., Conclusions: Use of chemical thromboprophylaxis in TBI patients with a stable or improved head CT after 24 hours substantially reduces the incidence of VTE and does not increase the risk of progression of intracranial hemorrhage., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to assess the effects of a localized anastomosis between the aorta and left lower lobe pulmonary artery on flows through central vessels and on the vascular reactivity of small pulmonary arteries distal or contralateral to the shunt., Methods: Flow rates in major vessels and tensions from small pulmonary arteries from the left and right lower lobes were determined 48 hours after creation of an end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta., Results: Anastomoses increased flow through the left lower lobe pulmonary artery from 194±6 to 452±18 mL/min immediately after anastomosis to 756±19 mL/min by the time of harvest (n=88, P<.05). Flow rates in main pulmonary arteries from hosts with anastomoses were lower (557±26 vs 1033±244 mL/min), whereas aortic root flows were not different from control values (1370±53 vs 1120±111 mL/min; P=.07). Wet/dry weights of both lungs and aortic flow rates were proportional to shunt flow rates. Pulmonary artery rings harvested from the right (unshunted) lobes of high-flow hosts exhibited increased reactivity to the thromboxane agonist U46619 and phenylephrine relative to those of left pulmonary arteries from the same animal or those of control hosts., Conclusions: Our studies are the first to identify enhanced reactivity of pulmonary arteries in a lung contralateral to a localized high-output shunt between an aorta and pulmonary artery. These observations suggest that patients with localized systemic-to-pulmonary shunt could exhibit modified vascular tone in remote pulmonary arteries., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Our model of a systemic-pulmonary shunt exhibits enhanced reactivity of pulmonary arteries contralateral to a localized shunt between the left lower lobe pulmonary artery and aorta relative to those of ipsilateral or control pulmonary arteries 48 hours after anastomosis. We examined the contribution of nitric oxide, cyclooxygenase, lipoxygenase, or cytochrome P450 production to mediating this enhanced reactivity., Methods: We created a surgical end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta. Forty-eight hours later, we tested tension of pulmonary artery rings from the right and left lower lobes for contraction to the thromboxane mimetic U46619 in the presence of vehicle or inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450, or lipoxygenase. Western blots of pulmonary artery homogenates were probed for endothelial nitric oxide synthase or isoforms metabolizing arachidonic acid. Eicosanoid products from intact pulmonary artery rings were detected using labeled arachidonic acid and high-performance liquid chromatography separation., Results: Enhanced reactivity of unshunted right pulmonary arteries over that of left pulmonary arteries from high-flow hosts was not eliminated by inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450. Treatment with 2 different lipoxygenase inhibitors, nordihydroguaiaretic acid and cinnamyl-3,4-dihydroxy-α-cyanocinnamate, closed the difference in contractility of shunted and unshunted pulmonary arteries. Pulmonary arteries contralateral to shunts metabolized arachidonic acid to 12-hydroxyeicosatetraenoic acid in greater quantities than analogous pulmonary arteries from the experimental left or control pulmonary arteries., Conclusions: Forty-eight hours after anastomosis, enhanced reactivity of contralateral pulmonary arteries is attributable in part to increased lipoxygenase products as opposed to nitric oxide or other eicosanoid products., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: This study determined the mechanisms and time-course of recovery of vascular relaxation in middle cerebral arteries (MCAs) of salt-fed Sprague-Dawley rats returned to a low-salt (LS) diet (0.4% NaCl) or infused with low-dose angiotensin II (ANG II)., Methods: Rats were fed a high-salt (HS) diet (4% NaCl) for 3 days or 4 weeks before returning to an LS diet for various periods. Other rats fed a HS diet (HS+ANG II) received a chronic (3 days) intravenous (i.v.) infusion of a low dose of ANG II (5 ng kg(-1) min(-1)) to prevent salt-induced ANG II suppression., Results: The HS diet eliminated the increase in cerebral blood flow in response to acetylcholine (ACh) infusion and the relaxation of MCA in response to ACh, iloprost, cholera toxin, and reduced PO2. Recovery of vascular relaxation was slow, requiring at least 2 weeks of the LS diet, regardless of the duration of exposure to a HS diet. Hypoxic dilation was mediated by cyclo-oxygenase metabolites and ACh-induced dilation was mediated via nitric oxide in LS rats and in HS rats returned to the LS diet or receiving ANG II infusion., Conclusions: Returning to a LS diet for 2 weeks or chronic 3-day ANG II infusion restores the mechanisms that normally mediate cerebral vascular relaxation.

Background: This study aimed to assess intermittent intravenous (IV) pantoprazole for control of gastric acid and the possible prevention of upper gastrointestinal (UGI) bleeding in intensive care units (ICU) patients., Methods: This was a multicenter, randomized, open-label, dose-ranging pilot study of IV pantoprazole (40 mg q24 hour; 40 mg q12 hour; 80 mg q24 hour; 80 mg q12 hour; 80 mg q8 hour) or continuously infused cimetidine (300 mg bolus; 50 mg/h) in patients at risk for UGI bleeding. The primary endpoint was percent time gastric pH >/=4.0. UGI bleeding and pneumonia were measured as secondary endpoints., Results: Two hundred two ICU patients were randomized. Gastric pH was well controlled by all treatments. Gastric pH control improved from day 1 to day 2 in all pantoprazole groups, whereas there was decreased pH control in the cimetidine group. There were no cases of protocol defined UGI bleeding in any treatment group. Adverse event frequency and pneumonia incidence were similar between pantoprazole and cimetidine treated patients., Conclusions: This pilot study indicates that intermittent IV pantoprazole effectively controls gastric pH and may protect against UGI bleeding in high risk ICU patients without the development of tolerance.

Background: Ambient levels of pesticides ("pesticide drift") are detectable at residences near agricultural field sites., Objective: Our goal was to evaluate the hypothesis that maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorders (ASD) in children., Methods: We identified 465 children with ASD born during 1996-1998 using the California Department of Developmental Services electronic files, and matched them by maternal date of last menstrual period to 6,975 live-born, normal-birth-weight, term infants as controls. We determined proximity to pesticide applications using California Department of Pesticide Regulation records refined using Department of Water Resources land use polygons. A staged analytic design applying a priori criteria to the results of conditional logistic regressions was employed to exclude associations likely due to multiple testing error., Results: Of 249 unique hypotheses, four that described organochlorine pesticide applications--specifically those of dicofol and endosulfan--occurring during the period immediately before and concurrent with central nervous system embryogenesis (clinical weeks 1 through 8) met a priori criteria and were unlikely to be a result of multiple testing. Multivariate a posteriori models comparing children of mothers living within 500 m of field sites with the highest nonzero quartile of organochlorine poundage to those with mothers not living near field sites suggested an odds ratio for ASD of 6.1 (95% confidence interval, 2.4-15.3). ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites., Conclusions: The association between residential proximity to organochlorine pesticide applications during gestation and ASD among children should be further studied.

Two previous large genetic linkage studies in the US population have implicated an area in chromosome 1p to contain a susceptibility gene for alcohol dependence. The 1-LOD support interval of the linkage signal spans about 30 cM and contains >30000000 DNA base pairs (bp) and 700 predicted genes. In order to reduce the size of the candidate area and potentially identify novel candidate genes within this region, we fine-mapped this area using closely spaced short tandem repeat (STR) markers and the transmission disequilibrium test (TDT) in small nuclear families. The subjects were 87 European-American families including one or more alcohol-dependent offspring (93 children and 174 parents). The initial marker set consisted of 30 STR markers, spanning the Marshfield map interval between 101.48 and 130.73 cM. Using the TDTPHASE program, we identified three markers in the distal part of this region (125-126 cM), which showed evidence of transmission disequilibrium. On the basis of this result, an additional 12 STR markers were genotyped in this region; some of these markers provided additional evidence for linkage disequilibrium. The strongest evidence for transmission disequilibrium was obtained at the marker D1S406 (P=0.005, 126.16 cM), with supporting evidence from three neighboring STR markers D1S424 (126.16 cM, P=0.01), D1S2804 (126.16 cM, P=0.04), and D1S2776 (126.16 cM, P=0.02), which are all located within a <350000 bp interval. These findings suggest that a gene (or genes) causing susceptibility to alcohol dependence resides near location 126.16 cM on chromosome 1. In addition, these results provide independent confirmation of the linkage finding regarding the identification of at least one gene in this region increasing the risk for alcohol dependence.

We recently reported localized increased pulmonary arterial resistance, neointimal lesions, and medial thickening induced by aortopulmonary anastomosis in young pigs. This model was used to investigate changes in expression of genes potentially involved in pulmonary vascular remodeling employing a high throughput Atlas Human Cardiovascular Array carrying approximately 600 cardiovascular-related cDNA sequences. Data were confirmed by Northern analysis, Western blots, and histological examination. With the use of lower stringency conditions for hybridization, 56% of the 588 human genes on the array showed visible signal after autoradiography. Approximately 10% of the genes with visible hybridization were altered by shunt-induced high flow. Extracellular matrix and cell adhesion molecules were the most highly represented group of upregulated genes. To our knowledge, our data are the first to demonstrate flow-induced changes in gene expression using a combination of cross species cDNA arrays, homologous hybridization, immunospecific protein, and histology. Our observations expand the list of genes as putative candidates in pulmonary vascular remodeling and support the utility of cross-species microarray analysis in such applications.

When thoracic aortic rupture is suspected, a 45-degree reverse Trendelenburg (RT) anteroposterior (AP) chest radiograph should place the mediastinal structures in a more appropriate position and allow a more accurate evaluation than a supine AP radiograph. One hundred ninety-one consecutive hemodynamically stable adult patients with major blunt thoracic trauma were initially evaluated for mediastinal abnormalities associated with aortic disruption by both supine AP chest radiograph and an AP chest radiograph with the patient in 45-degree RT position. One hundred four patients underwent contrast aortography based on mediastinal abnormalities detected on the supine AP chest radiograph. Twenty of these patients had abnormal aortograms demonstrating traumatic aortic disruption confirmed at surgery. Supine and RT chest radiographs were retrospectively compared in a blinded fashion to evaluate their specificity and positive predictive value for detection of traumatic thoracic aortic rupture. If RT chest radiographic findings had been used to determine the need for further assessment, 29 angiograms (26%) would have been eliminated, specificity would have increased from 52 per cent to 69 per cent, and positive predictive value would have increased from 19 per cent to 27 per cent. Both supine and RT chest radiographs demonstrated mediastinal widening in all 20 patients with abnormal aortograms, with no missed thoracic aortic disruptions (100% sensitivity). This study indicated that the RT chest radiograph may be used instead of the standard supine radiograph as the initial screen for mediastinal evaluation, maintaining a high sensitivity and eliminating the cost and morbidity of many unnecessary aortograms.

Adrenocortical cancers are relatively rare endocrine tumors that usually present when hormonally active or after they have become large and metastasis has occurred. Consequently, the 5-year survival rate is 20% to 35%. Surgical removal remains the only form of therapy proven to prolong survival. Mitotane is the most accepted form of chemotherapy. For the approximately 20% to 25% of patients whose tumors respond to mitotane, survival is prolonged.

The purpose of this review is to present a 4-year experience with the vacuum pack technique of temporary abdominal closure. From April 1992 to December 1996, 171 vacuum packs were performed on 93 patients. Eighty-seven vacuum packs were performed on 38 general surgical patients, and 84 vacuum packs were performed on 55 trauma patients. Overall hospital mortality was 32 per cent. Methods of achieving permanent wound closure varied in 73 patients. Four patients (4.3%) developed enterocutaneous fistulae; four patients developed intra-abdominal abscesses (4.3%). There were no eviscerations. Management of the complicated intra-abdominal process is discussed: 1) the decision to manage the abdomen in an open fashion; 2) which method of temporary closure to use; 3) subsequent explorations; 4) when the abdomen should be closed; 5) which type of closure to use; and 6) when the abdominal wall should be revised (herniorrhaphy). The vacuum pack is the method of choice for open abdomen management and temporary abdominal closure at our institution. With careful subsequent management, good patient outcome can be achieved.

Background: Experience in the treatment of patients with blunt colonic injuries is based on isolated case reports, and it is unclear whether the principles that guide the management of penetrating colonic injuries should be applied to these patients. Reviews of patients with these injuries suggest that such injuries present unique problems for diagnosis and treatment and are accompanied by excessive morbidity and mortality., Study Design: A 42-month retrospective case series was analyzed., Results: Data from 27 patients were analyzed, accounting for 8.5 percent of all colon and rectal injuries and for 0.5 percent of total blunt trauma admissions. Automobile crashes were the cause of injuries in 20 patients (74 percent). The mean Injury Severity Score was 28. All but 2 patients were operated on within 3 hours after admission. No significant difference was found in the morbidity and mortality rates based on the operation performed to manage the colonic injury. Indications for early exploration included a positive diagnostic peritoneal lavage in 23 patients, abnormal radiologic findings in 2, and positive clinical abdominal findings in the remaining 2 patients., Conclusions: Blunt colonic and rectal injuries are uncommon and pose problems for diagnosis and treatment. Associated injuries are common, and steering wheel compression of the upper abdomen as well as lap belts seem to predispose to colonic injuries. Initial diagnosis is made at the time of operation, and a thorough exploration of the abdominal cavity is important to diagnose associated injuries. Treatment must be individualized; however, based on our observations, the creation of ostomies is not mandatory for the treatment of these injuries.

Alkyl-lysophospholipids are analogues of 2-lysophosphatidylcholine which have been reported to have selective antitumor activity. A survey of the in vitro activity of racemic 1-octadecyl-2-methoxy-glycero-3 phosphorylcholine on in vitro clonogenicity in soft agar and tritiated thymidine incorporation was conducted on bone marrow specimens from a series of patients with acute myelogenous leukemia (AML) and chronic myelocytic leukemia (CML) and hematologically normal individuals. A dose- and time-dependent inhibition of colony formation and thymidine incorporation was observed in the normal and leukemic specimens. No selective effect of the compound could be demonstrated under the conditions employed in these studies.

Alkyl-lysophospholipids (ALP) are reported to be selectively cytotoxic to neoplastic cells and have been demonstrated to be an effective purging agent for autologous marrow transplantation in a murine model, WEHI-3B. We studied the effect of in vitro treatment of normal bone marrow cells with ALP and of cryopreservation on spleen colony-forming units (CFU-s) in irradiated, syngeneic Balb/c mice. We found that exposure of cells to doses of ALP of 5 or 20 micrograms/ml followed by cryopreservation had no effect on CFU-s, but that a dose of 100 micrograms/ml was toxic. A simulated remission marrow was prepared by mixing normal murine bone marrow cells with WEHI-3B myelomonocytic leukemic cells to give a 1%-2% concentration of leukemic cells. These were exposed to 0- to 100-micrograms/ml concentrations of ALP for 24 h, cryopreserved, thawed, and injected into the tail veins of lethally irradiated syngeneic mice, and survival measured. It was found that concentrations of ALP from 10 to 50 micrograms/ml resulted in long-term disease-free survivors. These results established the fact that cryopreservation did not alter the effectiveness of ALP in purging marrows of residual leukemic cells.

We developed a simplified, relatively rapid, inexpensive, antigen-nonspecific, enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG)- and C3-containing circulating immune complexes (CICs), adapted from a solid-phase anti-C3 radioimmunoassay (RIA). Standards (containing purified, heat-aggregated IgG and fresh human serum) or samples were allowed to react with goat F(ab')2 antihuman C3 bound to the matrix of microtiter plates. Then alkaline phosphatase conjugated to goat IgG fraction antihuman IgG was added, followed by p-nitrophenylphosphate, optical densities determined, and concentrations of CICs calculated. We found excellent correlations between serum and plasma CIC levels by either ELISA (r = 0.95, p less than 0.01) or RIA (r = 0.89, p less than 0.01). Furthermore, ELISA quantitation of CICs correlated well with RIA (serum, n = 75, r = 0.64, p less than 0.01; plasma, n = 101, r = 0.56, p less than 0.01). By ELISA we found 32 normal subjects had 38 +/- 12 micrograms CIC/ml in serum and 34 +/- 10 micrograms CIC/ml in plasma. Patients with systemic lupus erythematosus (39% of 27 patients, p less than 0.05) had significantly elevated CIC levels compared with normal (serum, 157 +/- 50 micrograms/ml, p less than 0.01; plasma, 89 +/- 23 micrograms/ml, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The selective cytocidal effect of alkyl lysophospholipids against neoplastic cells while sparing normal cells make these ideal candidates for purging leukemic cells from bone marrows obtained during remission. To test the feasibility of such an approach, a murine model and an in vitro human cell model were developed. In the murine system a mixture of normal bone marrow cells and WEHI IIIB myelomonocytic leukemic cells was incubated with varying doses of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-Me) for 24 hr before being injected into tail veins of lethally irradiated Balb/c mice. At doses of 20 and 100 micrograms/ml, long-term survivors were noted. The additional steps of freezing and thawing following incubation resulted in significantly longer survival with doses of 10 to 50 micrograms/ml, but were toxic to marrow stem cells at 100 micrograms/ml. In the in vitro model, normal marrow progenitor cells and leukemic cells (the promyelocytic cell line HL60) were exposed to varying concentrations of ET-Me for 1 and 4 hr alone or mixed, and clonogenicity was assayed by colony formation in semisolid medium during 7-14 days' incubation. At doses up to 100 micrograms/ml exposed for 4 hr normal progenitor cells were spared and HL60 colonies eliminated. Other phospholipids analogues were less effective in eliminating leukemic cells, but spared normal progenitor cells. A survey of fresh leukemic cells found varying degrees of sensitivity to ET-Me, indicating the need for testing a variety of compounds. These studies clearly indicated the potential usefulness of alkyl lysophospholipid compounds in selectively purging leukemic cells from remission marrows for autologous bone marrow transplantation.

Autologous bone marrow transplantation is potentially curative in the treatment of acute leukemia if residual leukemic cells in the marrow can be eliminated prior to transplantation. We studied the purging effects of a synthetic alkyl-lysophospholipid (ALP) on marrow containing leukemic cells from a transplantable myelomonocytic leukemia (WEHI-3B) in BALB/c mice. Simulated remission bone marrow containing 2% leukemic cells treated in vitro with 20 and 100 micrograms/mL of ET-18-OCH3 (1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine) significantly prolonged survival of lethally irradiated transplanted recipients. At a dose of 100 micrograms/mL, 88% of the mice survived for the duration of the experiment (approximately five months). Autopsies showed that 25% of these survivors had microscopic evidence of leukemia. Thus, in vitro treatment of marrow eliminated leukemic blasts and spared sufficient normal stem cells to allow hematologic reconstitution. The effect of ET-18-OCH3 is not entirely selective for leukemic cells. A spleen colony assay showed that ALP has some cytotoxic effect on normal hematopoietic stem cells.