Measurement of mid-calcaneal length on plain radiographs: reliability of a new method

The authors present a new method to reliably measure the length of the mid-portion of the calcaneus. The authors defined the "mid-calcaneal length" as the line connecting the high point of the convex arc of the posterior subtalar joint facet and the low point of the concave arc of the calcaneocuboid joint. Statistical analysis of 810 measurements taken by 6 observers confirmed high intraobserver reliability, interobserver reliability, and internal consistency (Cronbach coefficient α = .98) and low error rate (Pearson correlation coefficient = .0001). The authors have used this measurement as a tool to determine the change in calcaneal length after osteotomy lengthening procedures and present it as a tool for clinical practice and research.     

Dual kidney transplants from very old or very young donors: long-term outcomes and complications

The disparity between donors and the demand for organ transplants grows steadily. Annually, 4700 patients die on the kidney transplant waiting list in the United States. To increase utilization of deceased donor organs, we expanded our acceptable criteria to include very old (VO) or very young (VY) donors. We transplanted both such kidneys (dual transplant) into a single recipient and evaluated the long-term outcomes and complications. From July 2001 to December 2005, 16 patients (mean age 68, range 60-78) received dual kidneys from VO (mean age 72, range 60-79) donors and 6 patients (mean age 47, range 27-72) were transplanted from VY (mean age 17 months, range 2-36) donors. Seventy-four percent of these kidneys were imported after rejection by their local center due to low glomerular filtration rate (GFR) and extreme age. One- and 5-year patient survival rates were 100% and 88%, respectively. Death-censored 1- and 5-year graft survival rates for recipient of VO kidneys were 95% and 93%, and 66% and 50% for recipients of VY kidneys, respectively. Five-year graft survival rate for recipients of VO donor kidneys was 93% and was equal to the survival of standard deceased donor (SCD) kidney transplants (87%). The 5-year survival of dual transplants from VO donors was higher than expanded criteria deceased donor (ECD; P = .05). Over a mean follow-up of 66 ± 28 months, rejection rates were 10%, not statistically different than other groups. Of 22 dual transplants, four patients experienced urinary tract infections; three developed incisional subcutaneous seromas, and there were more urinary leaks compared to SCD (13.6% vs 2%, P = .002). The average 1- and 5-year estimated GFR (Cockcroft-Gault) was 57.4 and 54.6 mL/min, respectively. When properly placed in a single patient, such marginal organs are a valuable resource that offer comparable outcomes to SCD transplants and superior outcomes to ECD organs.     

Reliability and validity of the Safety Assessment Scale for people with dementia living at home

BACKGROUND: With the recent funding changes in health care services, more seniors with dementia are cared for in their homes and the nature of their condition puts them at higher risk for accidents and injuries. PURPOSE: The Safety Assessment Scale (SAS) was developed for use by community healthcare providers to evaluate and lower the risk of accidents, provide recommendations to family caregivers and enhance case management. Method. The scale was assessed in terms of the reliability as well as content, criterion and construct validity with 176 community-residing people with dementia in Quebec, Alberta and British Columbia. The Safety Assessment Scale was validated in French and English. RESULTS: The SAS demonstrated an excellent test-retest (ICC=.91) and inter-rater (ICC=.88) reliability. Results for validity were also extremely good. PRACTICE IMPLICATIONS: The scale is available in French and English. The short version of the SAS is a screening tool and the longer version provides an in-depth evaluation of safety and intervention planning. The SAS can be used by a variety of health care professionals who work with individuals who have dementia.     

Antecedent ethanol ingestion prevents postischemic microvascular dysfunction.

Prolonged ischemia followed by reperfusion (I/R) results in impaired endothelial cell function in all segments of the microvasculature. Moreover, microcirculatory dysfunction plays a major role in the genesis of the reperfusion component of total tissue injury in I/R. Thus, preservation of endothelial function is an important therapeutic goal for ameliorating injury in tissues subjected to I/R. An accumulating body of evidence indicates that low to moderate ethanol consumption produces an adaptive transformation to a protected phenotype in both microvascular endothelium and parenchymal cells such that they are rendered resistant to the pathologic effects of I/R. The purpose of this review is to summarize our current understanding of the signaling pathways underlying the development of the preconditioned state induced by antecedent ethanol in arteriolar, capillary, and venular endothelium. In addition, we will highlight understudied areas with regard to microvascular protection afforded by antecedent ethanol in the hopes that this will stimulate investigation of its underlying mechanisms. Understanding these signaling pathways may provide a mechanistic rationale for the development of novel treatment interventions that target both the microcirculatory and parenchymal sequelae to I/R, thereby maximizing the therapeutic potential of the protected phenotypes produced by pharmacologic preconditioning.     

A stimulus-responsive contrast agent for ultrasound molecular imaging

Complement activation by targeting ligands is an important issue that governs the fate of targeted colloidal contrast agents for molecular imaging. Here, we extend previous work on a stimulus-responsive microbubble construct, in which the ligand is normally buried by a polymeric overbrush and transiently revealed by ultrasound radiation force, to show reduced complement activation and focused adhesion to cells using a physiological peptide ligand. Attachment of C3/C3b in vitro and production of soluble C3a anaphylotoxin in vitro and in vivo decreased significantly for the buried-ligand architecture vs. the conventional exposed-ligand motif and no-ligand control. Additionally, the buried-ligand architecture prevented adhesion of Arg-Gly-Tyr (RGD)-bearing microbubbles to integrin-expressing human umbilical vein endothelial cells (HUVEC) when driven by buoyancy in a static chamber, but it did not affect adhesion efficiency when activated by ultrasound radiation force pulses. These results show, for the first time, the molecular mechanism for reduced immunogenicity for the buried-ligand architecture and feasibility of targeting with this motif using a physiological ligand-receptor pair.     

Induction of oxidative stress in Trypanosoma brucei by the antitrypanosomal dihydroquinoline OSU-40

Dihydroquinoline derivative OSU-40 (1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate) is selectively potent against Trypanosma brucei rhodesiense in vitro (50% inhibitory concentration [IC(50)], 14 nM; selectivity index, 1,700) and has been proposed to cause the formation of reactive oxygen species (ROS) in African trypanosomes (J. Fotie et al., J. Med. Chem. 53:966-982, 2010). In the present study, we sought to provide further support for the hypothesis that OSU-40 kills trypanosomes through oxidative stress. Inducible RNA interference (RNAi) was applied to downregulate key enzymes in parasite antioxidant defense, including T. brucei trypanothione synthetase (TbTryS) and superoxide dismutase B (TbSODB). Both TbTryS RNAi-induced and TbSODB RNAi-induced cells showed impaired growth and increased sensitivity toward OSU-40 by 2.4-fold and 3.4-fold, respectively. Decreased expression of key parasite antioxidant enzymes was thus associated with increased sensitivity to OSU-40, consistent with the hypothesis that OSU-40 acts through oxidative stress. Finally, the dose-dependent formation of free radicals was observed after incubation of T. brucei with OSU-40 utilizing electron spin resonance (ESR) spectroscopy. These data support the notion that the mode of antitrypanosomal action for this class of compounds is to induce oxidative stress.     

A pilot study to assess markers of renal damage in the rodent kidney after exposure to 7 MHz ultrasound pulse sequences designed to cause microbubble translation and disruption

Acoustic radiation force has been proposed as a mechanism to enhance microbubble concentration for therapeutic and molecular imaging applications. It is hypothesized that once microbubbles are localized, bursting them with acoustic pressure could result in local drug delivery. It is known that low-frequency, high-amplitude acoustic energy combined with cavitation nuclei can result in bioeffects. However, little is known about the bioeffects potential of acoustic parameters involved in radiation force and microbubble destruction pulse sequences applied at higher frequencies. In this pilot study, rat kidneys are exposed to high-duty cycle, low-amplitude pulse sequences known to cause substantial bubble translation due to radiation force, as well as high-amplitude short pulse sequences known to cause microbubble destruction. Both studies are performed at 7 MHz on a clinical ultrasound system, and implemented in three-dimensions (3-D) for entire kidney exposure. Analysis of biomarkers of renal injury and renal histopathology indicate that there was no significant renal damage due to these ultrasound parameters in conjunction with microbubbles within the study group.     

A plan for the handling of externally contaminated livestock

Nuclear accidents and access to radiological weapons for terrorist organizations and countries with hostile intentions towards the United States are realistic scenarios in the current global landscape. A dispersion of radionuclides can result from a nuclear weapon detonation or from a nuclear accident occurring in facilities handling or using radioactive material, such as nuclear power reactors. Any target of a radiological dispersal device (RDD) or an attack with a nuclear weapon and the surrounding area of a reactor accident could be subject to a significant amount of fallout and radioactive contamination. Therefore, a nuclear event in close proximity to agricultural areas will cause significant concern regarding the contamination of food products. In order to respond quickly and effectively to a large amount of contaminated agricultural products, such as livestock, a prepared and effective plan for handling and processing of these products is necessary. A protocol outlining the evaluation of and procedures for handling and processing radioactively contaminated livestock is proposed, to ensure safe animal food production and economic stability in the livestock industry in the wake of such a nuclear or radiological event. An evaluation of the salvageability of the contaminated livestock is performed based on the degree of exposure, the cost of decontamination, expected demand for food products, and economic impact to the owner/producer. Important factors that impact the salvageability of affected livestock are listed and analyzed to support the decision process for handling contaminated animals.     

Vaporization Detection Imaging: A Technique for Imaging Low-Boiling-Point Phase-Change Contrast Agents with a High Depth of Penetration and Contrast-to-Tissue Ratio

Phase-change contrast agents (PCCAs) possess advantages over microbubble contrast agents, such as the ability to extravasate and circulate longer in the vasculature that could enhance the diagnostic capabilities of contrast-enhanced ultrasound. PCCAs typically have a liquid perfluorocarbon (PFC) core that can be vaporized into echogenic microbubbles. Vaporization of submicron agents filled with liquid PFCs at body temperature usually requires therapeutic pressures higher than typically used for diagnostic imaging, but low-boiling-point PCCAs using decafluorobutane or octafluoropropane can be vaporized using pressures in the diagnostic imaging regime. Low-boiling-point PCCAs produce a unique acoustic signature that can be separated from tissue and bubble signals to make images with high contrast-to-tissue ratios. In this work, we explore the effect of pulse length and concentration on the vaporization signal of PCCAs and a new technique to capture and use the signals to make high contrast-to-tissue ratio images in vivo. The results indicate that using a short pulse may be ideal for imaging because it does not interact with created bubbles but still produces strong signals for making images. Furthermore, it was found that capturing PCCA vaporization signals produced higher contrast-to-tissue ratio values and better depth of penetration than imaging the bubbles generated by droplet activation using conventional contrast imaging techniques. The resolution of the vaporization signal images is poor because of the low frequency of the signals, but their high sensitivity may be used for applications such as molecular imaging, where the detection of small numbers of contrast agents is important.     

Assessment of Molecular Acoustic Angiography for Combined Microvascular and Molecular Imaging in Preclinical Tumor Models

Purpose

The purposes of the present study is to evaluate a new ultrasound molecular imaging approach in its ability to image a preclinical tumor model and to investigate the capacity to visualize and quantify co-registered microvascular and molecular imaging volumes.

Procedures

Molecular imaging using the new technique was compared with a conventional ultrasound molecular imaging technique (multi-pulse imaging) by varying the injected microbubble dose and scanning each animal using both techniques. Each of the 14 animals was randomly assigned one of three doses; bolus dose was varied, and the animals were imaged for three consecutive days so that each animal received every dose. A microvascular scan was also acquired for each animal by administering an infusion of nontargeted microbubbles. These scans were paired with co-registered molecular images (VEGFR2-targeted microbubbles), the vessels were segmented, and the spatial relationships between vessels and VEGFR2 targeting locations were analyzed. In five animals, an additional scan was performed in which the animal received a bolus of microbubbles targeted to E- and P-selectins. Vessel tortuosity as a function of distance from VEGF and selectin targeting was analyzed in these animals.

Results

Although resulting differences in image intensity due to varying microbubble dose were not significant between the two lowest doses, superharmonic imaging had significantly higher contrast-to-tissue ratio (CTR) than multi-pulse imaging (mean across all doses 13.98 dB for molecular acoustic angiography vs. 0.53 dB for multi-pulse imaging; p = 4.9 × 10^?10). Analysis of registered microvascular and molecular imaging volumes indicated that vessel tortuosity decreases with increasing distance from both VEGFR2- and selectin-targeting sites.

Conclusions

Molecular acoustic angiography (superharmonic molecular imaging) exhibited a significant increase in CTR at all doses tested due to superior rejection of tissue artifact signals. Due to the high resolution of acoustic angiography molecular imaging, it is possible to analyze spatial relationships in aligned microvascular and molecular superharmonic imaging volumes. Future studies are required to separate the effects of biomarker expression and blood flow kinetics in comparing local tortuosity differences between different endothelial markers such as VEGFR2, E-selectin, and P-selectin.