Citations

The Green's function approach describes propagating shear waves generated by an acoustic radiation force in elastic and viscoelastic soft tissue. Calculations with the Green's function approach are evaluated in elastic and viscoelastic soft tissue models for a line source and for a simulated focused beam. The results for the line source input are evaluated at 200 time samples in a 101 by 101 point grid that is perpendicular to the line source. For a shear wave speed of 1.4832 m/s and a compressional wave speed of 1500 m/s, shear wave simulations for a line source input in elastic and viscoelastic soft tissue models are completed in 431 and 2487 s with Matlab scripts, respectively, where the shear viscosity is 0.1 Pa.s in the viscoelastic model. Simulations are evaluated at a single point for an acoustic radiation force generated by a 128 element linear array operating at 4.09 MHz, and these simulations require 228 s and 1327 s for elastic and viscoelastic soft tissue models, respectively. The results show that these are effective models for simulating shear wave propagation in soft tissue, and plans to accelerate these simulations will also be discussed. [Supported in part by NIH Grants R01 EB012079 and R01 DK092255.]

Purpose Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain. Patients and Methods In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1. Results Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (−9.1) than for placebo (−4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and −2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study. Conclusion A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.

Interstitial cells of Cajal (ICC) act as pacemaker cells in the gastrointestinal tract by generating electrical slow waves to regulate rhythmic smooth muscle contractions. Intrinsic Ca 2+ oscillations in ICC appear to produce the slow waves by activating pacemaker currents, currently thought to be carried by the Ca 2+ -activated Cl − channel anoctamin 1 (Ano1). In this article we present a novel model of small intestinal ICC pacemaker activity that incorporates store-operated Ca 2+ entry and a new model of Ano1 current. A series of simulations were carried out with the ICC model to investigate current controversies about the reversal potential of the Ano1 Cl − current in ICC and to predict the characteristics of the other ion channels that are necessary to generate slow waves. The model results show that Ano1 is a plausible pacemaker channel when coupled to a store-operated Ca 2+ channel but suggest that small cyclical depolarizations may still occur in ICC in Ano1 knockout mice. The results predict that voltage-dependent Ca 2+ current is likely to be negligible during the slow wave plateau phase. The model shows that the Cl − equilibrium potential is an important modulator of slow wave morphology, highlighting the need for a better understanding of Cl − dynamics in ICC.

SummaryBackgroundVillous atrophy (VA) with intraepithelial lymphocytosis is the histological hallmark of coeliac disease (CD), but reported rates of mucosal recovery are variable.AimTo determine the impact of age and other demographic variables on the probability of persistent VA on follow‐up biopsy.MethodsWe identified patients with VA on duodenal histology at all 28 Swedish pathology departments during the years spanning 1969–2008. We examined age, gender, calendar period, duration of disease and educational attainment to determine predictors of persistent VA.ResultsOf 7648 patients with CD who underwent follow‐up biopsy, persistent VA was present in 3317 (43%; 95% CI 42–44%). The effect of age on persistent VA varied according to time period; among those biopsied in the years spanning 2000–2008, the prevalence of persistent VA was 31%, and increasing age was associated with increasing rates of persistent VA (17% among those younger than 2 years compared to 56% among those ≥70 years). In contrast, persistent VA did not vary widely by age in earlier years. On multivariate analysis (restricted to the calendar period 2000–2008, 2–5 years after CD diagnosis), persistent VA was more common among males (OR 1.43; 95% CI 1.07–1.90) and less common among patients with higher educational attainment (OR for college degree vs. <2 years of high school 0.52, 95% CI 0.35–0.78).ConclusionsThe prevalence of persistent villous atrophy has changed over time, with greater rates of healing in recent years. Social differences in persistent villous atrophy suggest that access and/or education regarding the gluten‐free diet impact mucosal healing.

Objective The objective of this article is to evaluate electrically evoked thresholds for cortical spreading depression (CSD) and stress-induced activation of trigeminal afferents in a rat model of medication-overuse headache (MOH). Methods Sumatriptan or saline was delivered subcutaneously by osmotic minipump for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were anesthetized and recording/stimulating electrodes implanted. The animals were pretreated with vehicle or topiramate followed by graded electrical stimulation within the visual cortex. CSD events were identified by decreased EEG amplitude and DC potential shift. Additional unanesthetized sumatriptan or saline-pretreated rats were exposed to bright light environmental stress and periorbital and hindpaw withdrawal thresholds were measured. Following CSD stimulation or environmental stress, immunohistochemical staining for Fos in the trigeminal nucleus caudalis (TNC) was performed. Results Sumatriptan pre-exposure significantly decreased electrical stimulation threshold to generate a CSD event. Topiramate normalized the decreased CSD threshold as well as stress-induced behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline-treated animals. Moreover, CSD and environmental stress increased Fos expression in the TNC of sumatriptan-treated rats, and these effects were blocked by topiramate. Environmental stress did not elicit cutaneous allodynia or elevate TNC Fos expression in saline-treated rats. Conclusions A previous period of sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD and environmental stress-induced activation of the TNC that was prevented by topiramate. Lowered CSD threshold, and enhanced consequences of CSD events (increased activation of TNC), may represent an underlying biological mechanism of MOH related to triptans.

Objective: We investigated ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif, member 13) messenger RNA levels as a biomarker of disease features in systemic lupus erythematosus. Methods: We measured and compared messenger RNA (mRNA) levels of ADAMTS13 in peripheral blood cells in patients with systemic lupus erythematosus and healthy control subjects by whole-genome microarray. We retrospectively analyzed the correlations of ADAMTS13 mRNA expression with clinical features, laboratory parameters, therapeutic features, and disease activity (according to the Systemic Lupus Erythematosus Disease Activity Index). We also examined the association of three single nucleotide polymorphisms (rs4962145, rs2285467, and rs685523) of the ADAMTS13 gene with patient characteristics. Results: In 309 patients, the median ADAMTS13 mRNA expression levels were significantly higher in blood cells of systemic lupus erythematosus patients than in 23 healthy controls ( p = .03). Notably, ADAMTS13 mRNA expression levels were significantly higher in systemic lupus erythematosus patients with a history of stroke ( p = .02) or transient ischemic attack ( p = .02). Among the three single nucleotide polymorphisms analyzed, rs2285467 was significantly associated with stroke ( p = .03) and anticardiolipin antibodies ( p = .04). Conclusions: Increased expression of ADAMTS13 mRNA in blood cells is associated with the presence of ischemic cerebrovascular disease in systemic lupus erythematosus patients and suggests a potential role for ADAMTS13 in the pathogenesis of ischemic cerebrovascular disease in these patients.