Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells.

It was previously reported that treatment with the sulfated polysaccharide fucoidan or the structurally similar dextran sulfate increased circulating mature white blood cells and hematopoietic progenitor/stem cells (HPCs) in mice and nonhuman primates; however, the mechanism mediating these effects was unclear. It is reported here that plasma concentrations of the highly potent chemoattractant stromal-derived factor 1 (SDF-1) increase rapidly and dramatically after treatment with fucoidan in monkeys and in mice, coinciding with decreased levels in bone marrow. In vitro and in vivo data suggest that the SDF-1 increase is due to its competitive displacement from heparan sulfate proteoglycans that sequester the chemokine on endothelial cell surfaces or extracellular matrix in bone marrow and other tissues. Although moderately increased levels of interleukin-8, MCP1, or MMP9 were also present after fucoidan treatment, studies in gene-ablated mice (GCSFR(-/-), MCP1(-/-), or MMP9(-/-)) and the use of metalloprotease inhibitors do not support their involvement in the concurrent mobilization. Instead, SDF-1 increases, uniquely associated with sulfated glycan-mobilizing treatments and not with several other mobilizing agents tested, are likely responsible. To the authors' knowledge, this is the first published report of disrupting the SDF-1 gradient between bone marrow and peripheral blood through a physiologically relevant mechanism, resulting in mobilization with kinetics similar to other mobilizing CXC chemokines. The study further underscores the importance of the biological roles of carbohydrates.     

Pulmonary surfactant as a vehicle for intratracheal delivery of technetium sulfur colloid and pentamidine in hamster lungs

Tracheal instillation of pentamidine in a surfactant vehicle may be an effective direct method of antibiotic delivery to the lungs. In 10 healthy hamsters, we compared the pulmonary distribution of 99mTc sulfur colloid (TcSC) mixed with pentamidine, using as a vehicle either surfactant (n = 5) or saline (n = 5). Each animal was instilled with 0.25 ml/kg of suspension containing 0.0018 mCi TcSC and pentamidine mixed with either surfactant or saline. After 4 h of spontaneous respiration, the lungs were excised, inflated to TLC, dried, and sliced into 3-mm cross sections from apex to base. Autoradiographs were examined to evaluate 99mTc distribution. The surfactant group had detectable radioactivity in 93% of all slices compared with 72% in the saline group (p = 0.02). Six slices per animal (43% of total) and their corresponding autoradiographs were analyzed for distribution of radioactivity. Lung slice area was determined by planimetry, and autoradiograph area was determined by video densitometry. We calculated the fraction of each lung slice with detectable radioactivity. The surfactant group had 41% of the lung slice areas exposed compared with 21% in the saline group (p = 0.02). The coefficient of variation of radioactive intensities within each slice was used as an index of spatial uniformity. There was a trend towards more uniform distribution in the surfactant group, with a narrower range of variation of intensities (1.51 to 2.56) than the saline group (1.95 to 6.47). We conclude that a surfactant vehicle significantly increases airspace deposition of TcSC and pentamidine instilled intratracheally in normal hamster lungs, and may improve uniformity of spread.     

Inability of dimethyl sulfoxide to increase brain uptake of water-soluble compounds: implications to chemotherapy for brain tumors

There is conflicting evidence as to whether dimethyl sulfoxide (DMSO) can reversibly open the blood-brain barrier and augment brain uptake of water-soluble compounds, including anticancer agents. To investigate this, 125I-human serum albumin, horseradish peroxidase, or the anticancer drug melphalan was administered iv to rats or mice, either alone or in combination with DMSO. Some animals received an additional ip priming dose of DMSO. The regional brain concentrations of each substance were measured after the animals were killed. DMSO administration did not significantly increase the brain uptake of any of the compounds as compared to control uptakes. These results do not support prior reports that DMSO increases the permeability of water-soluble agents across the blood-brain barrier.     

Integrated Cardiac and Lung Ultrasound (ICLUS) in the Cardiac Intensive Care Unit

Purpose of Review

This review highlights the use of basic lung ultrasound and introduces the concept of integrated cardiac and lung ultrasound (ICLUS) in the care of patients in the cardiac intensive care unit (ICU).

Recent Findings

Cardiac ultrasound is a fundamental imaging modality that is the gold standard for the diagnosis of cardiac pathology at the bedside. However, the demographics of the modern cardiac ICU are evolving to encompass patients with complex multi-organ system dysfunction in addition to acute cardiovascular disease. Therefore, a more comprehensive diagnostic approach is needed to allow the cardiologist to unravel the potential interplay of multiple pathologic processes. Literature on lung ultrasound has expanded dramatically in recent years as it has proven to be a feasible and accurate exam that provides rapid diagnosis of pulmonary pathology including pneumothorax, pleural effusion, pneumonia, and pulmonary edema. Furthermore, combined cardiac and lung sonography exposes the interaction of circulatory and pulmonary physiology that is central to the diagnosis and management of acute cardiovascular disease. ICLUS provides valuable information for the diagnosis and management of conditions such as respiratory failure, shock, and heart failure.

Summary

Numerous studies in recent years have illustrated the utility of lung ultrasound in various clinical settings. Integration of lung and cardiac ultrasound provides the cardiologist with a more holistic examination of the medically complex patients that are admitted to the modern cardiac ICU.

     

Using the wisdom of the crowds to find critical errors in biomedical ontologies: a study of SNOMED CT

Objectives The verification of biomedical ontologies is an arduous process that typically involves peer review by subject-matter experts. This work evaluated the ability of crowdsourcing methods to detect errors in SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to address the challenges of scalable ontology verification.Methods We developed a methodology to crowdsource ontology verification that uses micro-tasking combined with a Bayesian classifier. We then conducted a prospective study in which both the crowd and domain experts verified a subset of SNOMED CT comprising 200 taxonomic relationships.Results The crowd identified errors as well as any single expert at about one-quarter of the cost. The inter-rater agreement (κ) between the crowd and the experts was 0.58; the inter-rater agreement between experts themselves was 0.59, suggesting that the crowd is nearly indistinguishable from any one expert. Furthermore, the crowd identified 39 previously undiscovered, critical errors in SNOMED CT (eg, ‘septic shock is a soft-tissue infection’).Discussion The results show that the crowd can indeed identify errors in SNOMED CT that experts also find, and the results suggest that our method will likely perform well on similar ontologies. The crowd may be particularly useful in situations where an expert is unavailable, budget is limited, or an ontology is too large for manual error checking. Finally, our results suggest that the online anonymous crowd could successfully complete other domain-specific tasks.Conclusions We have demonstrated that the crowd can address the challenges of scalable ontology verification, completing not only intuitive, common-sense tasks, but also expert-level, knowledge-intensive tasks.     

HIV Care Outcomes in Relation to Racial Redlining and Structural Factors Affecting Medical Care Access Among Black and White Persons with Diagnosed HIV—United States, 2017

AIDS and Behavior - Black/African American (Black) versus White persons are unequally burdened by human immunodeficiency virus (HIV) in the United States. Structural factors can influence social...