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Purpose: To evaluate the characteristics and frequency of remission in pediatric patients with Graves’ disease (GD) treated with antithyroid drug (ATD) and to identify factors that may be associated with relapse.Methods: Medical records of patients younger than 19 years who presented to the Department of Pediatrics of Queen Elizabeth Hospital Hong Kong with newly diagnosed GD from 1st January 2007 to 31st December 2017 were retrospectively reviewed. Remission was defined as euthyroidism for 12 months or more after discontinuation of ATD treatment and no relapses during the follow-up period. Patients who successfully achieved remission were compared to those who suffered relapse. Factors that may predict occurrence of relapse after ATD treatments were studied, and their odds ratios (ORs) were calculated.Results: A total of 101 patients was included in this study. Eighty-one patients completed one course of ATD. Eighteen patients (17.8%) successfully achieved remission, and 58 patients (57.4%) experienced relapse after discontinuation of ATD. The remission group received a significantly longer course of ATD therapy than the relapse group (median, 28 months; interquartile range [IQR], 18–48 months in remission group vs. median, 21 months; IQR, 17–26; p=0.024). The OR for relapse was 0.971 (95% confidence interval [CI], 0.946–0.997) in univariate analysis and remained significant after adjustments in the multivariate regression model (OR, 0.961; 95% CI, 0.933–0.989; p=0.008).Conclusion: The remission rate in pediatric patients with GD treated with ATD was low. A longer ATD course was associated with a greater chance of remission in this population.

The Watershed Function Scientific Focus Area (WFSFA) is a U.S. Department of Energy research project that seeks to determine how mountainous watersheds retain and release water, carbon, nutrients, and metals. The WFSFA maintains a community field observatory at its primary field site in the East River, Colorado. The WFSFA collects diverse environmental data and has developed a “Field-Data” workflow that standardizes data management across the project, from field collection to laboratory analysis to publication. This workflow enables the WFSFA to address data quality and management challenges that environmental observatories face. Through this workflow, the WFSFA has increased the use of the data curated from the project by (1) providing detailed metadata with unique identifiers for samples, locations, and sensors, (2) streamlining the data sharing and publication process through early sharing of data internally within the team and publication of data on the ESS-DIVE repository following curation, and (3) adopting machine-readable and FAIR community data standards (Findability, Accessibility, Interoperability, Reusability). We describe an example application of this workflow for geochemical data, which utilizes a community geochemical data standard for water-soil-sediment chemistry (https://github.com/ess-dive-community/essdive-water-soil-sed-chem) developed by Environmental Systems Science Data Infrastructure for a Virtual Ecosystem (ESS-DIVE). This data standard is designed to standardize geochemical data, metadata, and file-level metadata, and was applied to WFSFA geochemical data, including ICP-MS, Isotope, Ammonia-N, Anion, DIC/NPOC/TDN datasets. This ensures important metadata is contained within the data file, such as precision of data analysis, storage and sample processing information, detailed sample names, material information, and unique identifiers associated with the samples (IGSNs). This metadata is essential to understand and reuse data products, as well as enable machine-readability for future model applications. Detailed examples of the standardized geochemical data types were created and are now being used as templates by WFSFA researchers to standardize their geochemical data. The adoption of this community geochemical data standard and more broadly the Field-Data workflow will improve the findability and reusability of WFSFA datasets.

Stress granules (SGs) form through phase separation of biomacromolecules to assist cells in resisting environmental stresses. Numbers of SG proteins contain Arg-Gly-Gly (RGG) motifs, indicating their RNA binding ability, and providing a substrate platform for asymmetric dimethylation of arginine (ADMA), whose roles in SG assembly remain unclear. Here, we demonstrated that Caprin1-mediated recruitment of PRMT1 asymmetrically dimethylates RGGs to provide multiple binding sites for TDRD3, a typical ADMA reader, which in turn bridges the multivalent interactions between RGG motifs and RNA to promote phase separation. This process was suppressed by a bivalent inhibitor of TDRD3, eventually inhibiting proliferation more effectively than arsenite treatment alone. Our work reveals the role of ADMA in SG assembly and the potential of targeting condensates for cancer therapy.

Diverse observational and simulation datasets are needed to understand and predict complex ecosystem behavior over seasonal to decadal and century time-scales. Integration of these datasets poses a major barrier towards advancing environmental science, particularly due to differences in the structure and formats of data provided by various sources. Here, we describe BASIN-3D (Broker for Assimilation, Synthesis and Integration of eNvironmental Diverse, Distributed Datasets), a data integration framework designed to dynamically retrieve and transform heterogeneous data from different sources into a common format to provide an integrated view. BASIN-3D enables users to adopt a standardized approach for data retrieval and avoid customizations for the data type or source. We demonstrate the value of BASIN-3D with two use cases that require integration of data from regional to watershed spatial scales. The first application uses the BASIN-3D Python library to integrate time-series hydrological and meteorological data to provide standardized inputs to analytical and machine learning codes in order to predict the impacts of hydrological disturbances on large river corridors of the United States. The second application uses the BASIN-3D Django framework to integrate diverse time-series data in a mountainous watershed in East River, Colorado, United States to enable scientific researchers to explore and download data through an interactive web portal. Thus, BASIN-3D can be used to support data integration for both web-based tools, as well as data analytics using Python scripting and extensions like Jupyter notebooks. The framework is expected to be transferable to and useful for many other field and modeling studies.

Microplastics (MPs) were characterized in surficial marine sediment (n = 36) and mussel (n = 29) samples collected along the British Columbia (BC) coast, Canada, using visual identification and Fourier Transform Infrared Spectrometry. MPs counts averaged 32.6 ± 5.3 particles per kg in sediment and 0.38 ± 0.04 particles per individual mussel (0.24 ± 0.04 /g of tissue). Victoria Harbour and the North Coast (Prince Rupert area) were MP hotspots, likely resulting from a combination of local sources and oceanographic conditions. Microfibers1000 μm dominated the pattern in both matrices (61.1 % in sediment; 65.4 % mussels) highlighting the suspected role of textiles in the widespread distribution of MPs in the marine environment. Overall, polyester was dominant in sediment and mussels (54.1 % and 63.5 %, respectively), followed by polyethylene (16.2 % and 11.5 %, respectively). This is the first report of MPs in sediment and mussels along the coast of BC using standardized methods.

We present a system for inductive program synthesis called DreamCoder, which inputs a corpus of synthesis problems each specified by one or a few examples, and automatically derives a library of program components and a neural search policy that can be used to efficiently solve other similar synthesis problems. The library and search policy bootstrap each other iteratively through a variant of "wake-sleep" approximate Bayesian learning. A new refactoring algorithm based on E-graph matching identifies common sub-components across synthesized programs, building a progressively deepening library of abstractions capturing the structure of the input domain. We evaluate on eight domains including classic program synthesis areas and AI tasks such as planning, inverse graphics, and equation discovery. We show that jointly learning the library and neural search policy leads to solving more problems, and solving them more quickly.

Purpose We sought to evaluate features of partial remission (PR) in children with type 1 diabetes mellitus (T1DM) using the insulin-dose adjusted A1c (IDAA1c) definition and to identify risk factors associated with nonremission. Methods Medical records of patients with newly diagnosed T1DM between January 1, 2008, and June 30, 2018, were retrospectively reviewed. Hemoglobin A1c (HbA1c) readings and insulin total daily doses (TDDs) of each patient at each follow-up visit were obtained with IDAA1c values calculated. PR was defined as an IDAA1c score of 9 points or less within 6 months of diagnosis. The trends of HbA1c and TDD within 2 years after diagnosis were compared between remitters and nonremitters. Factors that may predict the occurrence of PR were studied, with their relative risks of nonremission calculated. Results PR occurred in 26 patients (45.6%), including 8 girls and 18 boys, with a median duration of 8 months. The frequency of remission in male patients was significantly higher (P=0.002) and the relative risk of female sex with nonremission was 2.20 (95% confidence interval [CI], 1.24-3.91), which remained significant when adjusted by multivariate regression modeling. The initial HbA1c level at diagnosis was also significantly higher in the nonremission group (P=0.029), with a relative risk of 1.12 (95% CI, 1.01-1.25). Both HbA1c (P=0.012) and TDD (P=0.006) were significantly lower within 2 years after diagnosis among remitters than in nonremitters. TDD was significantly lower in male patients (P=0.029) during the same period, while there was no significant difference in HbA1c level between male and female patients (P=0.163). Conclusion Both the initial HbA1c level at diagnosis and sex were factors associated with the occurrence of PR. Female sex was an independent risk factor of nonremission, likely resulting from a higher insulin requirement in female T1DM patients.

This article describes an innovative application of a social justice-infused pedagogy to an out-of-school program for urban high school students. Using an interdisciplinary framework, the program featured a coherent synthesis of science, technology, engineering, and math (STEM) education, highlighting environmental and food justice perspectives; social justice education; and career and college planning. We used qualitative content analysis to analyze two separate interviews with six female and three male students of color ranging in age from 15 to 18 with an average age of 16.1 (SD=1.26) across an approximately 10-month time span. Utilizing a model of critical consciousness development as our organizing framework, we explored the students’ understanding of environmental and food justice issues. Participants indicated that they were actively engaged in learning about food and environmental justice, exploring STEM careers, and investigating the various ways that social justice is manifested in their lives. Implications for social justice and STEM education interventions as well as broader public policies are discussed.

Background: Obesity in pediatric and adolescent population has reached a universal pandemic. This study aimed to summarize the literature on the longest available outcome of bariatric surgery in morbidly obese adolescents. Methods :A systematic review was conducted to pool available data on the longest available (> 3 years) weight loss and comorbidity resolution outcome in adolescent bariatric surgery. Results: A total of 14 studies reporting the result of bariatric surgery after 3 years in 950 morbidly obese adolescents were included. Preoperative age and BMI ranged from 12 to 19 years and from 26 to 91 kg/m(2), respectively. Females were the predominant gender (72.8%). Laparoscopic roux-en-Y gastric bypass (n = 453) and adjustable gastric banding (n = 265) were the most common bariatric procedure performed. The number of patients at the latest follow-up was 677 (range from 2 to 23 years). On average, patients lost 13.3 kg/m(2) of their BMI. Among comorbidities, only diabetes mellitus resolved or improved dramatically. Of 108 readmissions, 91 led to reoperation. There was a weight regain

Representation and computation are the best tools we have for explaining intelligent behavior. In our program, we explore the space of representations present in the mind by constraining them to explain data at multiple levels of analysis, from behavioral patterns to neural activity. We argue that this integrated program assuages Brette's worries about the study of the neural code.

Structural aluminum alloys are used in marine applications where light weight and increased speed are paramount. The 5xxx series alloys are the ideal choice, providing an optimum combination of as-welded strength and general corrosion resistance. A particular concern is sensitization in service. Aluminum is considered sensitized when a nearly continuous network of β phase forms along the grain boundaries. The β phase is anodic to the Al matrix, and, when exposed to sea water and sufficient loading, provides a clear pathway to stress corrosion cracking (SCC). The degree of β-phase precipitation is driven by a combination of time and elevated temperature. For over a decade, SCC of Al superstructures has plagued Navy ships. To address this issue, relevant technologies have been adopted, adapted, and developed to combat this issue. More specifically, the technology areas involve the detection of sensitization, the mitigation of SCC, and the replacement of corrupt materials. The technologies discussed herein a...

As high-strength thinner-steel implementation in ship designs increase, dimensional management becomes critical to control construction costs and schedule in ship production. In the U.S. shipbuilding industry, improvements to shipbuilding facilities and processing technology have not kept pace with the rate of change in ship design. Additionally, new designs using thinner steels are subject to legacy weld sizing criteria possibly leading to inappropriately sized welds on lightweight materials. These two factors result in widespread overwelding, causing severe plate deformation in naval vessels during construction and nonvalue added labor to correct as needed for fit-up tolerances. Historically, shear and fatigue strength data has been focused on the larger welds and thicker steel plates typical of the state of the practice when these legacy weld sizing criteria were developed. In order to optimize weld design and production in modern, lightweight naval surface vessels, there is a need to develop more accurate data about the performance of precision fillet welds for thin steels.

This economic evaluation study examines the authors’ experience of prescribing tafamidis in terms of their cost and the insurance status of patients.

Simulation is an important alternative to evaluate cricothyrotomy, a rare life-saving procedure. This crossover study aimed to determine whether contextualization of a crisis scenario would impact the performance of a cricothyrotomy procedural task. Sixty-five anesthesia assistants and emergency medicine and anesthesia residents underwent a teaching session in surgical cricothyrotomy using one of two sets of cricothyrotomy kits: the Portex 6.0 and Melker 3.5 (n = 32) or the Portex 6.0 and Melker 5.0 (n = 33). Within six weeks following the session, the participants performed cricothyrotomies on a full-body patient mannequin simulator coupled with a porcine larynx (tissue-mannequin simulator) using the assigned two kits in a “cannot intubate, cannot ventilate” (CICV) contextualized scenario (CS) and in a CICV verbalized non-contextualized scenario (NCS). Each participant performed a total of four cricothyrotomies using the two kits in the two scenarios. The primary outcome measure was insertion time, and secondary outcome measures were severity of injuries and failure rate. Outcome measures were compared between scenarios for each kit. Mean (SD) insertion time for a successful cricothyrotomy was not significantly different between NCS and CS for the Melker 3.5 [83.0 (45.0) sec vs 63.3 (36.1) sec, respectively; P = 0.96; mean difference (MD), 19.7 sec; 95% confidence interval (CI), −1.9 to 41.3], the Melker 5.0 [86.5 (36.8) sec vs 107.1 (55.6) sec, respectively; P = 0.11; MD, −20.6 sec; 95% CI, −44.9 to 3.7], and the Portex 6.0 [59.5 (35.5) sec vs 59.0 (35.0) sec, respectively; P = 0.95; MD, 0.5 sec; 95% CI, −13.2 to 14.2]. Failure rate and severity of injuries, measured as mean average injury score for each kit, were also similar between scenarios. Contextualization of a crisis scenario did not affect the performance of a cricothyrotomy procedural task on a tissue-mannequin simulator. These findings may have implications when considering the feasibility and cost-effectiveness for assessing the performance of cricothyrotomy procedural tasks.

As high-strength thin-steel use in ship design increases, dimensional management becomes critical to control construction costs and schedule in ship production. In the U.S. shipbuilding industry, improvements to shipbuilding facilities and processing technology have not kept pace with the rate of change in ship design. Additionally, new designs using thinner steels are subject to legacy weld-sizing criteria, which may inappropriately size welds on lightweight materials. These two factors result in widespread overwelding, causing severe plate buckling in naval vessels during construction. The problem of overwelding has two distinct sources:the weld-sizing methods developed in the 1980s are still used in most shipbuilding specifications regardless of ship class. This prevents the incentive of application of latest technologies that can make strong, precision fillet welds for modern lightweight thin steel naval surface combatants; andshipyard welders tend to make welds even larger than design requirements to satisfy naval production specifications, which do not allow for any undersized welds. On average, production welds are 3 mm larger than design, which can more than double the heat input and distortion caused by welding. The approach to the solution of this overwelding problem will be described in detail in this article:develop appropriate weld-sizing criteria for thin plate structures; this can be facilitated by numerical modeling to ensure adequate static shear, tensile, bending, fatigue, and dynamic impact capacity of structural welds; andperform a robust designed experiment to establish confidence that small weld sizes can provide necessary performance and strength to meet the design service life of the vessel and provide data to NAVSEA technical warrant holders to support the implementation of an underweld tolerance for ship production to prevent overwelding.

La nouvelle loi sur la protection des majeurs, votee en mars 2007, permet-elle de mieux proteger les majeurs vulnerables que la loi de 1968 et si oui comment ? Offre-t-elle des garanties pour le respect de la volonte de la personne protegee, evite-t-elle les spoliations d’argent par des tuteurs ou des curateurs peu scrupuleux ? Le mandat de protection future, qui est la grande nouveaute de cette loi, participe-t-il concretement a cette volonte de rendre de la liberte au majeur vulnerable ? C’est a ces questions que nous tentons de repondre, apres quelques mois de mise en application de la nouvelle loi qui est entree en vigueur le 1er janvier 2009. Ces reflexions sont le fruit de notre pratique de medecin specialiste inscrit sur la liste etablie par le procureur de la republique de Paris et de medecin psychiatre au service de patients âges et souvent desorientes.

The apparent slip effects of laminar water flow in smooth hydrophobic microchannels and patterned hydrophobic microchannels were investigated. A series of experiments were performed to demonstrate the drag reductions for laminar water flow in hydrophobic microchannels. These microchannels were fabricated from silicon wafers using photolithography and were coated with hydrophobic octadecyltrichlorosilane (OTS). To generate a larger drag reduction, the patterned hydrophobic microchannels were fabricated to allow the liquid to flow over a region of trapped air in the cavity between the microridges. With the geometrical dimensions used, pressure drop reductions ranging from 10 to 30 % were found in the smooth microchannels and patterned microchannels. The pressure drop reduction was shown to increase with increasing microridge spacing and decreasing microchannel width. Using micro-particle image velocimetry (PIV), we measured an apparent slip velocity at the wall of approximately 8 % of the centerline velocity, yielding a slip length of approximately 2 μm in the smooth hydrophobic microchannel. Theoretically, the analytical solution derived for three-dimensional flow in a rectangular duct is presented to predict the slip velocity and slip length at the wall based on the pressure drop measurement. These results are in agreement with the experimental data obtained using micro-PIV.

The Construction Industry Review Report has highlighted the recent spate of non-compliant construction incidents in Hong Kong, which has prompted widespread public concern on the quality of construction projects. Whilst public housing has received special attention due to extensive coverage in the media, the quality of private housing has seldom been put under the spotlight, thereby raising the question as to whether private sector works are of better quality than public sector works.Faced with this question and the increasing drive towards benchmarking in the construction industry, it appears that an objective measure of quality is necessary, both for providing feedback to designers and for raising the quality standards of construction works. Being inspired by the benefits brought about by the CONQUAS system in Singapore, the Housing Authority in Hong Kong had developed and implemented the PASS system for benchmarking workmanship quality in the public housing sector since 1990. As yet, there has ...

The records of 141 consecutive patients with proven tuberculosis (TB) were reviewed to examine for changes in their serum proteins, erythrocyte sedimentation rate (ESR) and tuberculin skin test reactivity. Hypoalbuminaernia was present in 73% of patients and hyperglobulinaentia was seen in 92% of patients. ESR showed a negative correlation with the serum albumin level but a positive correlation with the serum globulin level. In the case of pulmonary TB, ESR was higher in patients with radiologically more extensive disease. Tuberculin reactivity was reduced in patients who were older, those with more severe Iiypoalbuininaemia and those with disseminated TB.

As high-strength thin-steel usage in ship design increases, dimensional management becomes very critical to control rework costs and schedule delays in ship production. Prior Office of Naval Research (ONR) and National Shipbuilding Research Program (NSRP) projects have helped Ingalls Shipbuilding to emphasize dimensional control for thin steel structures. Huntington-Ingalls (previous Northrop Grumman Shipbuilding) has, in recent years, substantially increased its emphasis on dimensional management as an enabler to achieving its aggressive goals for the future. These goals include cost and lead time reduction for hull erection and increasing early-stage outfitting. Nevertheless, improvements to shipbuilding facilities and process technology have not kept pace with the rate of change in ship design. Worse, new designs using thinner steels are subject to legacy weld size requirements. These two factors result in widespread overwelding. Severe plate buckling in naval vessels has been attributed to oversized welds in thin plate ship structures. The problem of overwelding has two distinct sources: - The weld sizing method developed in the 1980s is still used in most shipbuilding specifications regardless of ship class. This prevents the incentive of application of latest technologies that can make strong, precision fillet welds for modern lightweight thin steel naval surface combatants. - Shipyard welders tend to make welds even larger than design requirement in order to satisfy Quality Assurance (QA) inspection. In a number of investigations, fillet welds requiring a leg size of 5mm are typically found to have an average size of 8mm, resulting in more than double the heat input and distortion. The approach to the solution of this overwelding problem will be described in detail in this paper: - Develop appropriate weld sizing criteria for thin plate structures-this can be facilitated by numerical modeling to ensure adequate static shear, tensile, bending, fatigue and dynamic impact capacity of structural welds; - Perform a robust designed experiment to confirm the models and establish confidence that precision weld sizes can provide necessary performance and strength throughout the design service life of the vessel.

Determining the chromosomal phase of pairs of sequence variants – the arrangement of specific alleles as haplotypes – is a routine challenge in molecular genetics. Here we describe Drop-Phase, a molecular method for quickly ascertaining the phase of pairs of DNA sequence variants (separated by 1-200 kb) without cloning or manual single-molecule dilution. In each Drop-Phase reaction, genomic DNA segments are isolated in tens of thousands of nanoliter-sized droplets together with allele-specific fluorescence probes, in a single reaction well. Physically linked alleles partition into the same droplets, revealing their chromosomal phase in the co-distribution of fluorophores across droplets. We demonstrated the accuracy of this method by phasing members of trios (revealing 100% concordance with inheritance information), and demonstrate a common clinical application by phasing CFTR alleles at genomic distances of 11–116 kb in the genomes of cystic fibrosis patients. Drop-Phase is rapid (requiring less than 4 hours), scalable (to hundreds of samples), and effective at long genomic distances (200 kb).

Aim: (i) To determine the ability of general practitioners (GPs) and paediatricians to correctly identify children as overweight or obese by visual cues alone; (ii) to describe the current management practices of overweight and obese children by these practitioners; and (iii) to compare these with National Health and Medical Research Council (NHMRC) Clinical Practice Guidelines. Methods: Forty-four GPs and 29 paediatricians participated in the study. Respondents completed a questionnaire based on a series of body images, rating the size of the child as acceptable weight, overweight or obese and indicating the likelihood of carrying out a series of management options. Results: There was considerable variation in ability to rate images correctly with the total number of correct responses being 72% and 68%, respectively, for GPs and paediatricians. There were statistically significant differences in management between GPs and paediatricians in terms of conducting appropriate anthropometry and screening for co-morbidities, with paediatricians performing closer to the NHMRC Clinical Practice Guidelines. Conclusion: GPs and paediatricians have the opportunity to screen children for overweight and obesity during their everyday practice. Accurate determination of weight status cannot be performed by visualisation alone and all children should have height and weight measured and correctly interpreted. Some areas of current GP and paediatrician management of overweight and obese children fall short of the NHMRC clinical guidelines and areas for improvement are highlighted in this paper.

In [1], Dieter an Mey proposes the addition of an AUTO attribute to the OpenMP DEFAULT clause. A DEFAULT(AUTO) clause would cause the compiler to automatically determine the scoping of variables that are not explicitly classified as shared, private or reduction. While this new feature would be useful and powerful, its implementation would rely on automatic parallelization technology, which has been shown to have significant limitations. In this paper, we implement support for the DEFAULT(AUTO) clause in the Polaris parallelizing compiler. Our modified version of the compiler will translate regions with DEFAULT(AUTO) clauses into regions that have explicit scopings for all variables. An evaluation of our implementation on a subset of the SPEC OpenMP Benchmark Suite shows that with current automatic parallelization technologies, a number of important regions cannot be statically scoped, resulting in a significant loss of speedup. We also compare our compiler's performance to that of an Early Access version of the Sun Studio 9 Fortran 95 compiler [2].

Compliance with MARPOL environmental regulations has required the design of a waste management system to reduce the volume of solid shipboard waste and treat it so that it is safe to carry aboard ship. The U.S. Navy in cooperation with industry has developed a conceptual design of a plasma arc waste destruction system (PAWDS) capable of meeting strict shipboard weight, size, and operation criteria that has precluded the use of traditional commercial systems. The innovative system design has involved a thorough examination of candidate materials that should be capable of withstanding the processing of a variable waste stream that may include highly corrosive constituents. The structural components of the PAWDS should insure safety of personnel and ship by resisting degradation through high temperature corrosion, erosion, thermal cycling, and other effects.

• We tested the hypothesis that the increased permeability in the pulmonary microcirculation seen with endotoxin is caused by the release of oxygen radicals from activated neutrophils. We first compared the pulmonary injury in sheep caused by low-dose endotoxin with that produced by phorbol myristate acetate, an agent that selectively causes the release of oxygen radicals from neutrophils. We then determined the degree of lung tissue lipid peroxidation, a reflection of direct oxygen radical damage after endotoxin and phorbol myristate acetate. Both agents produced a nearly identical increase in protein permeability; however, peroxidation was only evident with phorbol myristate acetate. Higher doses of endotoxin did result in increased lung peroxidation as well as a more severe physiologic injury. We can conclude that oxygen radical release, most likely from neutrophils, occurs with endotoxin. However, the permeability injury may not be the direct result of increased lipid peroxidation, as increased permeability can be seen without measurable increases in this parameter. ( Arch Surg 1984;119:77-82)

Our purpose was, in general, to determine the effect of a body burn on the pulmonary response to endotoxemia and, specifically, to determine whether increased thromboxane (TxA2) production by the burn wound was responsible for the accentuated lung injury. Thirty-two unanesthetized sheep with lung and soft tissue lymph fistulae were studied. Twelve sheep were given a sublethal dose of intravenous E. coli endotoxin (2 micrograms/kg). A characteristic two-phase injury was noted as evidenced by early pulmonary hypertension and hypoxia and later increased lung permeability. TxA2 was significantly increased in lung lymph as well as aortic plasma relative to venous plasma, indicating the lung to be the source. Twelve of 12 sheep survived. Five of 13 sheep died from endotoxemia when given 3-5 days after a 25% total body surface (TBS) burn and five of seven died with endotoxin (2 micrograms/kg) and a 50% burn. Physiologic parameters were at preburn levels before endotoxin. Animals died both during the early phase from hypoxia and the later phase due, in large part, to increasing pulmonary dysfunction. Absolute levels of TxA2 were not increased in the postburn animals, nor was there a clear release of TxA2 from burn tissue to explain the accentuated response. Prostacyclin levels were, however, less elevated in postburn animals in response to endotoxin, thereby altering the TxA2/PGI2 ratio in favor of TxA2. However, a cause and effect relationship between the increased lung injury and TxA2 remains undetermined. Lymph flow or lymph protein content was not altered in burn tissue in response to endotoxin.

The formation and release of circulating chemoattractants has been considered to be responsible for the initial pulmonary leukostasis and subsequent pulmonary vascular injury seen with endotoxemia. Oxygen radicals released from granulocytes can produce these factors. Our purpose was (1) to determine whether chemotaxins are released with endotoxemia and whether the lung is the source of these factors and (2) if there is a cause and effect relationship between the release of chemoattractants and the lung injury. Lung lymph flow, QL, lymph protein clearance, and vascular pressures were used to monitor lung vascular integrity. Escherichia coli endotoxin was infused into 12 sheep. Six sheep were pretreated with dimethyl thiourea (DMTU), a scavenger of hydroxide ion radicals. Chemotactic activity (CA) of plasma and lung lymph was determined during baseline, the pulmonary hypertensive phase, and the permeability phase of the lung injury. It was found that endotoxemia was associated with generation of a granulocyte chemotactic factor in plasma but not in lung lymph. The peak increase in plasma CA occurred after the early pulmonary leukostasis. Pretreatment with DMTU eliminated the increased CA but had no effect on the initial leukopenia or the lung injury. It was concluded that (1) the lung is not the major source of increased CA after endotoxin and (2) increased plasma CA occurs but does not appear to be causative of the initial pulmonary leukostasis or the granulocyte-induced lung injury.

Our purpose was to determine whether peripheral soft tissues produce and release prostanoids in response to local sepsis, and whether this mediator release can produce pulmonary dysfunction. Escherichia coli endotoxin (2 micrograms/kg in 100 mL of saline) was injected below the hide of the flank in seven unanesthetized sheep. In three additional sheep, ibuprofen (12.5 mg/kg of body weight) was injected with the endotoxin. Thromboxane B2 and 6-keto-PGF1 alpha (prostacyclin) levels were measured in tissue lymph draining the flank, lung lymph, pulmonary artery (Ppa), and aortic plasma. One hour after endotoxin administration, mean PaO2 decreased from 90 to 74 mm Hg and Ppa increased from 22 to 35 mm Hg. Lung lymph flow (QL) increased only 50% with QL being protein poor. No increase in lung or peripheral soft-tissue vascular permeability was noted. Tissue lymph (TxB2) increased from 220 +/- 114 to greater than 10,000 pg/mL with levels in Ppa plasma increasing from 300 +/- 128 to 595 +/- 124 pg/mL and aortic plasma from 270 +/- 141 to 410 +/- 104 pg/mL. Lung lymph TxB2 paralleled aortic values. Peak levels of 6-keto-PGF1 alpha in systemic lymph exceeded 2,000 pg/mL while levels in lung lymph remained relatively constant. The pulmonary injury and the increase in TxB2 was prevented by ibuprofen. We conclude that the response of soft tissue to local endotoxin is to release thromboxane in quantities sufficient to raise plasma levels and to produce hypoxia and pulmonary hypertension. The lung dysfunction is not produced by an increase in lung water or vascular permeability.