Citations

The objective of this study was to analyze and optimize the ultrasound radiation force source for creating shear waves for quantitative elasticity and viscosity measurements. A simulation model based on work by Bercoff et al., [IEEE Trans. Ultrason. Ferroelectr. Freq. Contr. 51(11), 1523–34 (2004)] was utilized to examine the shear wave propagation from a spatiotemporal impulsive force and the simulated radiation force generated from a linear array transducer. Parameters such as aperture size, F-number of the transducer, and medium shear elasticity and viscosity were varied to analyze how the shear wave amplitude and shape changes. The wave attenuation and group and phase velocities were evaluated. The aperture size and the F-number of the transducer affected the spatial distribution of the propagating shear wave significantly. The influence of the coupling term between the bulk and shear waves was analyzed spatially and temporally by evaluating parameters such as shear wave amplitude, wave attenuation, and the group and phase velocities. This simulation model provides insight for making shear wave propagation measurements from the perspective of optimizing the spatial and temporal characteristics of induced shear wave motion from an applied radiation force. [This work was supported in part by Grant EB002167 from NIH.]

Although intelligibility deficits are common across various forms of dysarthria, it was hypothesized that the causes of intelligibility reductions depend on the ways the degraded signal challenges listener cognitive-perceptual strategies. This hypothesis was confirmed by analyzing the lexical boundary errors (LBE) elicited by 44 speakers with one of four forms of dysarthria (ataxic, hypokinetic, hyperkinetic, mixed spastic-flaccid). Error patterns from 60 listener transcripts revealed reliance on metrical stress to segment the 80 six-syllable phrases. However, reductions and disturbances in the acoustic cues to syllabic stress associated with each form of dysarthria resulted in different LBE patterns. Explanations for these unique patterns are found, in part, in the metrical structures of the dysarthric speech. For example, the temporal relationships among stressed and unstressed syllables varied widely in hyperkinetic speech, which ostensibly prevented listeners from optimally exploiting metrical stress as a cue for segmentation. The equal-even temporal structure of the spastic-flaccid speech resulted in the highest proportion of boundary insertions. The presence of interword pauses facilitated the assignment of word onset to strong syllables. Results will be presented relative to models of lexical segmentation and clinical implications for targets of remediation in the dysarthrias. [Work supported from NIH-NIDCD 5R01 DC6859.]

No particular regimen is considered standard therapy for widespread metastatic melanoma, although surgery is the primary choice for regional nodal metastases. Systemic interleukin-2 (IL-2) is an effective immunotherapy for melanoma, but standard doses are associated with severe toxicity. We report a patient who was treated with intralesional low-dose IL-2 and V-beam pulsed dye laser for the treatment of scalp melanoma metastases. This treatment resulted in rapid regression of metastatic tumors with limited adverse effects.

AbstractSirolimus is used in heart transplant patients with CAV and CNI‐induced nephropathy. However, little is known regarding the tolerability, rejection rate, and effect on renal function when used empirically in children. We describe our experience with the empiric use of a sirolimus‐based immunosuppressive regimen in pediatric heart transplantation recipients. We reviewed records of patients in whom conversion was attempted to a CNI‐free sirolimus‐based regimen. Rejection episodes and measures of renal function were recorded. We attempted to convert 20 patients, of which 16 were successful. In total, six of 20 patients (30%) experienced adverse effects. Of the 16 converted, four patients converted to sirolimus due to CNI‐induced disease (three nephropathy, one CAV), while 12 patients (mean age 5.5 yr, range 0.1–21 yr; 33% female; 33% with a history of congenital heart disease) were empirically switched to sirolimus at a mean of 2.3 yr after transplant. Follow‐up was available for a mean of 2.5 yr after conversion (range 0.5–8.3 yr). The rate of rejection while taking CNIs was 0.18 rejection episodes per patient‐year (total of five episodes), compared with 0.03 rejection episodes per patient‐year (total of one episode) while on sirolimus. Renal function, in terms of GFR, significantly improved after sirolimus conversion at latest follow‐up (from 86 ± 37 mL/min to 130 ± 49 mL/min, p = 0.02). Here, we demonstrate the potential benefit of empiric use of sirolimus in pediatric heart transplant patients in a CNI‐free regimen. Larger and longer studies are needed to further clarify risks of rejection and adverse effect profiles.

Polycythemia vera (PV) is currently diagnosed by the World Health Organization (WHO) criteria regarding hemoglobin (HB) levels and JAK2V617F and related mutations or by the British Committee for Standards in Haematology (BCSH) guidelines predominantly based on hematocrit (HCT) values (>52% in men and >48% in women) in JAK2 mutated patients. We examined clinical features at diagnosis and outcome in 397 mutated PV patients showing a bone marrow (BM) morphology conforming with the WHO descriptions but including also cases with a HB level <18.5 g/dL in males (range 16.0–18.4) and <16.5 g/dL in females (range 15.0–16.4). These patients were regarded as masked PV (mPV) comprising 140 (35%) cases of our cohort. A comparison with the BCSH criteria based on HCT levels revealed a decrease of mPV patients to 59 (15%). In both classification systems, mPV patients were more males, presented more frequently with higher platelet counts, and increased BM reticulin fibrosis. A worsening of overall survival was documented in mPV patients in comparison with overt PV following the WHO (P = 0.011) as well as the BCSH (P = 0.0019) criteria. Risk factors for inferior survival in mPV were age >65 years and white blood cell count >15 × 109/L. Without these risk factors mPV patients had the same survival as overt PV suggesting that a fraction of patients with HB lower than that required for WHO diagnosis should still be considered as overt PV. This study has established the existence of mPV by two different classification systems based on either HB or HCT threshold values. Am. J. Hematol. 89:199–202, 2014. © 2013 Wiley Periodicals, Inc.

Background— Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF), but its clinical profile and impact on exercise capacity remain unclear. RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized trial testing the impact of sildenafil on peak V O 2 in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm (SR) or AF. Methods and Results— RELAX enrolled 216 patients with HFpEF, of whom 79 (37%) were in AF, 124 (57%) in SR, and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing, echocardiogram, biomarker assessment, and rhythm status assessment before randomization. Patients with AF were older than those in SR but had similar symptom severity, comorbidities, and renal function. β-blocker use and chronotropic indices were also similar. Despite comparable left ventricular size and mass, AF was associated with worse systolic (lower EF, stroke volume, and cardiac index) and diastolic (shorter deceleration time and larger left atria) function compared with SR. Pulmonary artery systolic pressure was higher in AF. Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide for type I collagen levels, suggesting more severe neurohumoral activation, myocyte necrosis, and fibrosis. Peak V O 2 was lower in AF, even after adjustment for age, sex, and chronotropic response, and V E /V CO 2 was higher. Conclusions— AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity. These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00763867.

New FindingsWhat is the central question of this study?Patients with heart failure often develop ventilatory abnormalities at rest and during exercise, but the mechanisms underlying these abnormalities remain unclear. This study investigated the influence of inhibiting afferent neural feedback from locomotor muscles on the ventilatory response during exercise in heart failure patients.What is the main finding and its importance?Our results suggest that inhibiting afferent feedback from locomotor muscle via intrathecal opioid administration significantly reduces the ventilatory response to exercise in heart failure patients.Patients with heart failure (HF) develop ventilatory abnormalities at rest and during exercise, but the mechanism(s) underlying these abnormalities remain unclear. We examined whether the inhibition of afferent neural feedback from locomotor muscles during exercise reduces exercise ventilation in HF patients. In a randomized, placebo‐controlled design, nine HF patients (age, 60 ± 2 years; ejection fraction, 27 ± 2%; New York Heart Association class 2 ± 1) and nine control subjects (age, 63 ± 2 years) underwent constant‐work submaximal cycling (65% peak power) with intrathecal fentanyl (impairing the cephalad projection of opioid receptor‐sensitive afferents) or sham injection. The hypercapnic ventilatory response was measured to determine whether cephalad migration of fentanyl occurred. There were no differences in hypercapnic ventilatory response within or between groups in either condition. Despite a lack of change in ventilation, tidal volume or respiratory rate, HF patients had a mild increase in arterial carbon dioxide () and a decrease in oxygen (;P< 0.05 for both) at rest. The control subjects demonstrated no change in,, ventilation, tidal volume or respiratory rate at rest. In response to fentanyl during exercise, HF patients had a reduction in ventilation (63 ± 6versus44 ± 3 l min−1,P< 0.05) due to a lower respiratory rate (30 ± 1versus26 ± 2 breaths min−1,P< 0.05). The reduced ventilation resulted in lower(97.6 ± 2.5versus79.5 ± 3.0 mmHg,P< 0.05) and increased(37.3 ± 0.9versus43.5 ± 1.1 mmHg,P< 0.05), with significant improvement in ventilatory efficiency (reduction in the ventilatory equivalent for carbon dioxide;P< 0.05 for all). The control subjects had no change in ventilation or measures of arterial blood gases. These data suggest that inhibition of afferent feedback from locomotor muscle significantly reduces the ventilatory response to exercise in HF patients.