1004-57 Regional Left Ventricular Function by Intraventricular Ultrasound in Patients with Myocardial Infarction

Regional left ventricular (LV) dysfunction induced by ischemia/infarction is accompanied by increased end-systolic stress because the ischemic LV wall is unable to generate enough tension to contribute effectively to systole. To explore the possibility of assessing regional LV dysfunction as changes in LV wall stress we performed intraventricular echocardiography in 10 patients with a 6.2 french/12.5MHZ catheter at the time of cardiac catheterization. Cross-sectional images obtained at the level of the papillary muscles were analyzed by computer aided system to assess left ventricular wall thickness and radius of curvature (RC) in 16 equi-angular segments. End-systolic segmental endocardial radius of curvature divided by LV wall thickness obtained as segment area divided by the average of endo and epicardial arc lengths was utilized as an index of regional LV performance proportional to segmental LV wall stress. Percent wall thickening (WT%) was reduced (20.7±14.5%) in the territory perfused by the stenosed artery determined at catheterization, when compared with WT% obtained from territory perfused by normal coronaries (34.4±15.8%, p<0.05). In addition, systolic wall thickening was inversely related to the ratio of RC to WT at end-systole (r=0.75, %WT=65.5 – 21.4 (RCIWT), p<0.05) reflecting regional systolic dysfunction with increased circumferential end-systolic wall stress in those regions. In conclusion, intraventricular echocardiography correctly detects regional left ventricular dysfunction and its geometric consequences to local LV performance induced by ischemic myocardial damage. This technique may play an important role in monitoring myocardial injury by ischemia during invasive interventional procedures

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

Forces associated with launch into space do not impact bone fracture healing

Segmental bone defects (SBDs) secondary to trauma invariably result in a prolonged recovery with an extended period of limited weight bearing on the affected limb. Soldiers sustaining blast injuries and civilians sustaining high energy trauma typify such a clinical scenario. These patients frequently sustain composite injuries with SBDs in concert with extensive soft tissue damage. For soft tissue injury resolution and skeletal reconstruction a patient may experience limited weight bearing for upwards of 6 months. Many small animal investigations have evaluated interventions for SBDs. While providing foundational information regarding the treatment of bone defects, these models do not simulate limited weight bearing conditions after injury. For example, mice ambulate immediately following anesthetic recovery, and in most cases are normally ambulating within 1-3 days post-surgery. Thus, investigations that combine disuse with bone healing may better test novel bone healing strategies. To remove weight bearing, we have designed a SBD rodent healing study in microgravity (µG) on the International Space Station (ISS) for the Rodent Research-4 (RR-4) Mission, which launched February 19, 2017 on SpaceX CRS-10 (Commercial Resupply Services). In preparation for this mission, we conducted an end-to-end mission simulation consisting of surgical infliction of SBD followed by launch simulation and hindlimb unloading (HLU) studies. In brief, a 2 mm defect was created in the femur of 10 week-old C57BL6/J male mice (n = 9-10/group). Three days after surgery, 6 groups of mice were treated as follows: 1) Vivarium Control (maintained continuously in standard cages); 2) Launch Negative Control (placed in the same spaceflight-like hardware as the Launch Positive Control group but were not subjected to launch simulation conditions); 3) Launch Positive Control (placed in spaceflight-like hardware and also subjected to vibration followed by centrifugation); 4) Launch Positive Experimental (identical to Launch Positive Control group, but placed in qualified spaceflight hardware); 5) Hindlimb Unloaded (HLU, were subjected to HLU immediately after launch simulation tests to simulate unloading in spaceflight); and 6) HLU Control (single housed in identical HLU cages but not suspended). Mice were euthanized 28 days after launch simulation and bone healing was examined via micro-Computed Tomography (µCT). These studies demonstrated that the mice post-surgery can tolerate launch conditions. Additionally, forces and vibrations associated with launch did not impact bone healing (p = .3). However, HLU resulted in a 52.5% reduction in total callus volume compared to HLU Controls (p = .0003). Taken together, these findings suggest that mice having a femoral SBD surgery tolerated the vibration and hypergravity associated with launch, and that launch simulation itself did not impact bone healing, but that the prolonged lack of weight bearing associated with HLU did impair bone healing. Based on these findings, we proceeded with testing the efficacy of FDA approved and novel SBD therapies using the unique spaceflight environment as a novel unloading model on SpaceX CRS-10

Rapid prototyping of patterned functional nanostructures

Living systems exhibit form and function on multiple length scales, and the prospect of imparting life-like qualities to man-made materials has inspired many recent efforts to devise hierarchical materials assembly strategies. For example, Yang et al. grew surfactant-templated mesoporous silica on hydrophobic patterns prepared by micro-contact printing {micro}CP{sup 3}. Trau et al. formed oriented mesoporous silica patterns, using a micro-molding in capillaries MIMIC technique, and Yang et al. combined MIMIC, polystyrene sphere templating, and surfactant-templating to create oxides with three levels of structural order. Overall, great progress has been made to date in controlling structure on scales ranging from several nanometers to several micrometers. However, materials prepared have been limited to oxides with no specific functionality, whereas for many of the envisioned applications of hierarchical materials in micro-systems, sensors, waveguides, photonics, and electronics, it is necessary to define both form and function on several length scales. In addition, the patterning strategies employed thus far require hours or even days for completion. Such slow processes are inherently difficult to implement in commercial environments. The authors have combined evaporation-induced (silica/surfactant) self-assembly EISA with rapid prototyping techniques like pen lithography, ink-jet printing, and dip-coating on micro-contact printed substrates to form hierarchically organized structures in seconds. In addition, by co-condensation of tetrafunctional silanes (Si(OR){sub 4}) with tri-functional organosilanes ((RO){sub 3}SiR{prime}){sup 12--14} or by inclusion of organic additives, the authors have selectively derivatized the silica framework with functional R{prime} ligands or molecules. The resulting materials exhibit form and function on multiple length scales: on the molecular scale, functional organic moieties are positioned on pore surfaces, on the mesoscale, monosized pores are organized into 1-, 2-, or 3-dimensional networks, providing size-selective accessibility from the gas or liquid phase, and on the macroscale, 2-dimensional arrays and fluidic or photonic systems may be defined

Demand for Prophylaxis after Bioterrorism-Related Anthrax Cases, 2001

In 1991, most physicians in Minnesota and Wisconsin managed patients concerns about anthrax without dispensing prophylactic antimicrobial agents

A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators.

BACKGROUND: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes. METHODS: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later. RESULTS: The patients who underwent stenting had a higher rate of procedural success than those who underwent standard balloon angioplasty (96.1 percent vs. 89.6 percent, P = 0.011), a larger immediate increase in the diameter of the lumen (1.72 +/- 0.46 vs. 1.23 +/- 0.48 mm, P \u3c 0.001), and a larger luminal diameter immediately after the procedure (2.49 +/- 0.43 vs. 1.99 +/- 0.47 mm, P \u3c 0.001). At six months, the patients with stented lesions continued to have a larger luminal diameter (1.74 +/- 0.60 vs. 1.56 +/- 0.65 mm, P = 0.007) and a lower rate of restenosis (31.6 percent vs. 42.1 percent, P = 0.046) than those treated with balloon angioplasty. There were no coronary events (death; myocardial infarction; coronary-artery bypass surgery; vessel closure, including stent thrombosis; or repeated angioplasty) in 80.5 percent of the patients in the stent group and 76.2 percent of those in the angioplasty group (P = 0.16). Revascularization of the original target lesion because of recurrent myocardial ischemia was performed less frequently in the stent group than in the angioplasty group (10.2 percent vs. 15.4 percent, P = 0.06). CONCLUSIONS: In selected patients, placement of an intracoronary stent, as compared with balloon angioplasty, results in an improved rate of procedural success, a lower rate of angiographically detected restenosis, a similar rate of clinical events after six months, and a less frequent need for revascularization of the original coronary lesion

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe