Preparation and structural characterization of amorphous spray-dried dispersions of tenoxicam with enhanced dissolution

Tenoxicam is a poorly soluble nonsteroidal anti-inflammatory drug. In this work, the solubility of tenoxicam is enhanced using amorphous spray-dried dispersions (SDDs) prepared using two molar equivalents of l-arginine and optionally with 10%-50% (w/w) polyvinylpyrrolidone (PVP). When added to the dispersions, PVP is shown to improve physical properties and also assists in maintaining supersaturation in solution. The dispersions provide a twofold increase over equilibrium solubility at the same pH. The dispersions are characterized using electron microscopy, vibrational spectroscopy, diffuse-reflectance visible spectroscopy, and X-ray powder diffraction. The structures of the dispersions are probed using solid-state nuclear magnetic resonance (SSNMR) experiments applied to the (1) H, (13) C, and (15) N nuclei, including two-dimensional dipolar correlation experiments that detect molecular association and the formation of a glass solution between tenoxicam, l-arginine, and PVP. Other aspects of the amorphous structure, including hydrogen-bonding interactions and the ionization state of tenoxicam and l-arginine, are also explored using SSNMR methods. These methods are used to show that the SDDs contain an amorphous l-arginine salt of tenoxicam in a glass solution that also includes PVP when present. Finally, the dispersions show only a minor decrease in chemical stability during accelerated stability studies relative to a crystalline form of tenoxicam.     

Static and Dynamic Cumulative Maximum Intensity Display Mode for Subharmonic Breast Imaging

Objective. The purpose of this study was to test the efficacy of static and dynamic cumulative maximum intensity (CMI) subharmonic imaging (SHI) in breast ultrasound studies. Methods. Contrast‐enhanced SHI was performed in 14 women using a modified LOGIQ 9 scanner (GE Healthcare, Milwaukee, WI) transmitting/receiving at 4.4/2.2 MHz. Following mammography, baseline scans of gray scale ultrasound and power Doppler imaging (PDI) were performed. Contrast‐enhanced PDI and gray scale SHI were performed after contrast agent administration. Static CMI‐SHI is a composite image summarizing blood flow over multiple frames using the maximum intensity projection technique. The dynamic CMI‐SHI mode depicts the gradual inflow pattern of the contrast agent in blood vessels. Both CMI‐SHI modes were set up using a new automated sum‐absolute‐difference–based block‐matching algorithm to reduce noise and blurring and compensate for motion artifacts. Evaluation of the imaging modes for detecting breast cancer was done by an experienced radiologist, blinded to histopathologic findings. Sensitivity, specificity, and receiver operating characteristic (ROC) analyses were computed and compared for all ultrasound imaging modes and mammography. Results Of the 16 lesions, 4 were malignant. The area under the ROC curve (A_z) for the diagnosis of breast cancer was 0.64 for gray scale and PDI, 0.67 for contrast‐enhanced PDI, 0.76 for mammography, 0.78 for SHI, and 0.75 for static CMI‐SHI. For the dynamic CMI‐SHI mode, the A_z increased to 0.90, and this was significantly better than mammography (P = .03). Conclusions. The new dynamic CMI‐SHI mode produced the highest A_z for the diagnosis of breast cancer compared to conventional techniques and thus appears to improve diagnosis of breast cancer relative to conventional techniques, albeit based on a limited patient population.     

Current Epidemiology of Revision Total Knee Arthroplasty in the United States

Background

Revision surgery for failed total knee arthroplasty (TKA) continues to pose a substantial burden for the United States healthcare system. The predominant etiology of TKA failure has changed over time and may vary between studies. This report aims to update the current literature on this topic by using a large national database. Specifically, we analyzed: (1) etiologies for revision TKA; (2) frequencies of revision TKA procedures; (3) various demographics including payer type and region; and (4) the length of stay (LOS) and total charges based on type of revision TKA procedure.

Risk Factors and Costs Associated With Clostridium difficile Colitis in Patients With Prosthetic Joint Infection Undergoing Revision Total Hip Arthroplasty

Background

With the increased demand for primary total hip arthroplasty (THA) and corresponding rise in revision procedures, it is imperative to understand the factors contributing to the development of Clostridium difficile colitis. We aimed to provide a detailed analysis of: (1) the incidence of; (2) the demographics, lengths of stay, and total costs for; and (3) the risk factors and mortality associated with the development of C. difficile colitis after revision THA.

Constitutive Modeling of Liver Tissue: Experiment and Theory

Realistic surgical simulation requires incorporation of the mechanical properties of soft tissue in mathematical models. In actual deformation of soft-tissue during surgical intervention, the tissue is subject to tension, compression, and shear. Therefore, characterization and modeling of soft-tissue in all these three deformation modes are necessary. In this paper we applied two types of pure shear test, unconfined compression and uniaxial tension test to characterize porcine liver tissue. Digital image correlation technique was used to accurately measure the tissue deformation field. Due to gravity and its effect on the soft tissue, a maximum stretching band was observed from the relative strain field on sample undergoing tension and pure shear test. The zero strain state was identified according to the position of this maximum stretching band. Two new constitutive models based on combined exponential/logarithmic and Ogden strain energy were proposed. The models are capable to represent the observed non-linear stress–strain relation of liver tissue for full range of tension and compression and also the general response of pure shear.     

Response of adipose tissue to early infection with Trypanosoma cruzi (Brazil strain)

Brown adipose tissue (BAT) and white adipose tissue (WAT) and adipocytes are targets of Trypanosoma cruzi infection. Adipose tissue obtained from CD-1 mice 15 days after infection, an early stage of infection revealed a high parasite load. There was a significant increase in macrophages in infected adipose tissue and a reduction in lipid accumulation, adipocyte size, and fat mass and increased expression of lipolytic enzymes. Infection increased levels of Toll-like receptor (TLR) 4 and TLR9 and in the expression of components of the mitogen-activated protein kinase pathway. Protein and messenger RNA (mRNA) levels of peroxisome proliferator-activated receptor γ were increased in WAT, whereas protein and mRNA levels of adiponectin were significantly reduced in BAT and WAT. The mRNA levels of cytokines, chemokines, and their receptors were increased. Nuclear Factor Kappa B levels were increased in BAT, whereas Iκκ-γ levels increased in WAT. Adipose tissue is an early target of T. cruzi infection.     

Non-Invasive Intra-cardiac Pressure Measurements Using Subharmonic-Aided Pressure Estimation: Proof of Concept in Humans

This study evaluated the feasibility of employing non-invasive intra-cardiac pressure estimation using subharmonic signals from ultrasound contrast agents in humans. This institutional review board–approved proof-of-concept study included 15 consenting patients scheduled for left and right heart catheterization. During the catheterization procedure, Definity was infused intra-venously at 4–10 mL/min. Ultrasound scanning was performed with a Sonix RP using pulse inversion, three incident acoustic output levels and 2.5-MHz transmit frequency. Radiofrequency data were processed and subharmonic amplitudes were compared with the pressure catheter data. The correlation coefficient between subharmonic signals and pressure catheter data ranged from ?0.3 to ?0.9. For acquisitions with optimum acoustic output, pressure errors between the subharmonic technique and catheter were as low as 2.6 mmHg. However, automatically determining optimum acoustic output during scanning for each patient remains to be addressed before clinical applicability can be decided.