Citations

ABSTRACTTransgenic expression of the RNA-dependent RNA polymerase 3Dpolinhibited infection of Theiler's murine encephalitis virus (TMEV), a picornavirus from which it was derived. Here, we infected 3Dpoltransgenic mice with another picornavirus, as well as an alphaherpesvirus and a rhabdovirus. 3Dpoltransgenic FVB mice had significantly lower viral loads and survived longer after infection with all three types of viruses than nontransgenic FVB mice. Viral inhibition among three different types of virus by transgenic 3Dpolsuggests that the mechanism of action is not the direct interference with picornaviral 3Dpolbut instead may be the changing of host cells to an antiviral state before or after viral infection occurs, as basal interferon levels were higher in 3Dpoltransgenic mice before infection. Further study of this mechanism may open new possibilities for future antiviral therapy.

Arterial elasticity has gained importance in the past decades as it has been shown to be an independent predictor of cardiovascular diseases. Ultrasound radiation force has been used to excite propagating waves in arterial vessels in order to measure the wave speeds and characterize the elastic properties of the vessels. Excised pig carotid arteries were excited with impulsive radiation force using 3-MHz tonebursts of length 200, and the propagating waves were measured along the length of the artery over a distance of 2 cm. A 2-D fast Fourier transform was performed on the spatiotemporal data for identification of several propagating modes in the vessel. Multiple propagating modes could be visualized from the spatiotemporal data that varied with the transmural pressure of the artery under investigation over a range of 10–100 mm Hg. The modes present in the data were fitted with a theoretical model to estimate the elasticity of the arteries. The comparison with the model provides insight into characterizing the elastic properties of the artery. [This work was supported in part by NIH Grant no. EB002640.]

Vibro-acoustography with rectilinear raster scanning using confocal or linear array transducers have been reported before. Endo-cavity imaging requires a different type of scanning due to space limitation. This paper describes 3-D endo-cavity vibro-acoustography by a rotating linear array that scans the volume of interest. In this configuration a linear array is used to steer the beam electronically, which is combined with the rotational motion of the transducer to scan the beam in a cylindrical volume. This particular geometry produces special artifacts in the image. One such artifact is non-uniformity in signal power due to angular variations with respect to the hydrophone. Another artifact is related to the geometrical distortion in the image. In this paper, we will present examples of vibro-acoustography images with linear and rotational scanning and describe image characteristics and methods to reduce the artifacts. [Work supported by NIH Grant P50 CA91956P2.]

Characterization of viscoelastic soft tissues and materials has been a subject of active research for the past two decades. Techniques involving measuring the motion of embedded spheres in viscoelastic media have been employed to measure the viscoelastic material properties of the media surrounding the sphere. The published work using this technique has been restricted to using the Kelvin–Voigt model, which has worked for gelatin-based materials. We report an extension of this method using different viscoelastic rheological models such as the Maxwell, generalized Maxwell, Zener, and Kelvin–Voigt fractional derivative models. We performed experiments using a focused 3-MHz transducer to produce radiation force and a 7.5-MHz pulse-echo transducer to measure the sphere motion. Two phantoms were tested; one made of gelatin and another made of rubber with stainless steel spheres embedded in the materials. The response was fitted with the generalized theoretical model to find the material properties over bandwidths of 25–3000 Hz. The median absolute errors ranged from 0.0036–0.0421 and 0.0365–0.0879 for the gelatin and rubber phantoms, respectively. This generalized method offers added flexibility to characterize different types of viscoelastic materials using the most appropriate rheological model. [Work supported in part by NIH Grant nos. EB002167 and DK082408.]

Abstract There is growing interest in the use of mesenchymal stem cells for bone repair. As a major reason for normal bone remodeling is the removal of fatigue microcracks, advances in our understanding of this process may inform approaches to enhance fracture healing. Increasing evidence now indicates that physiological bone remodeling occurs in close proximity to blood vessels and that these vessels carry perivascular stem cells that differentiate into osteoblasts. Similarly, fracture healing is critically dependent on the ingrowth of blood vessels not only for a nutrient supply but also for the influx of osteoblasts. A number of animal and human studies have now shown the potential benefit of bone marrow-derived mesenchymal stem cells in enhancing bone repair. However, as in other tissues, the question of whether these cells improve fracture healing directly by differentiating into osteoblasts or indirectly by secreting paracrine factors that recruit blood vessels and the accompanying perivascular stem cells remains a major unresolved issue. Moreover, CD34+ cells, which are enriched for endothelial/hematopoietic cells, have also shown efficacy in various bone repair models, at least in part due to the induction of angiogenesis and recruitment of host progenitor cells. Thus, mesenchymal and nonmesenchymal stem/progenitor cells are attractive options for bone repair. It is possible that they contribute directly to bone repair, but it is also likely that they express paracrine factors in the appropriate amounts and combinations that promote and sustain the healing process.

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

PurposeTo determine whether increased duration of radiation therapy (RT) and overall treatment (RX) time has a detrimental effect in anal cancer.Patients and MethodsData from Radiation Therapy Oncology Group (RTOG) 87-04 and RTOG 98-11 trials were combined to form three treatment groups: RT/fluorouracil (FU)/mitomycin (n = 472), RT/FU/cisplatin (n = 320), and RT/FU (n = 145). Cox proportional hazards models were used with the following variables: RT duration, RT intensity, RX duration, treatment group, age, sex, Karnofsky performance score (KPS), T stage, N stage, and RT dose.ResultsIn the univariate analysis, there was a significant association between RX duration and colostomy failure (CF; hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.14; P = .02), local failure (HR = 1.52; 95% CI, 1.14 to 2.03; P = .005), locoregional failure (HR = 1.51; 95% CI, 1.15 to 1.98; P = .003), and time to failure (HR = 1.40; 95% CI, 1.10 to 1.79; P = .007). The significance of RX duration was maintained after adjusting for treatment group. In multivariate modeling there was a trend toward an association between RX duration and CF (HR = 1.57; 95% CI, 0.98 to 2.50; P = .06) and a statistically significant association with local failure (HR = 1.96; 95% CI, 1.34 to 2.87; P = .0006). Age, sex, KPS, T stage, N stage, and RT dose, but not RT duration, RT intensity, or RX duration, were found to be statistically significant predictors of OS and colostomy-free survival.ConclusionTotal treatment time, but not duration of radiation therapy, seems to have a detrimental effect on local failure and colostomy rate in anal cancer. Induction chemotherapy may contribute to local failure by increasing total treatment time.