Treatment of keloids using 5‐fluorouracil in combination with crystalline triamcinolone acetonide suspension: evaluating therapeutic effects by using non‐invasive objective measures

Background Intralesional 5‐fluorouracil (5‐FU) in combination with triamcinolone acetonide (TAC) has been recommended as a promising alternative for keloids not responding to silicone‐based products, cryotherapy or intralesional corticosteroids alone. Although numerous studies support the efficacy of this regime, there is a lack of objective data. Objectives In this study, we evaluate the therapeutic effect of four courses of intralesional 5‐FU in combination with TAC (3 : 1) utilizing 3D analysis (PRIMOS®pico), ultrasound and scar scales such as the Patient and Observer Scar Assessment Scales (POSAS) and the Dermatology Life Quality Index (DLQI). Methods Twenty‐five patients with keloids were treated using 5‐FU and TAC every 4 weeks. Objective assessments were performed and the scar scales administered at baseline, as well as during consecutive visits at 1‐ and 12‐month follow‐up (FU). Routine laboratory tests were performed at baseline and at 1‐month FU. Results 3D PRIMOS and ultrasound measurements revealed highly significant and stable reductions in height (baseline mean score: 4.0 ± 1.7 mm, 1‐month FU mean score: 1.5 ± 0.8 mm, 12‐month FU mean score: 1.8 ± 0.9 mm, P = <0.0001), volume (baseline mean score: 1,105 ± 911.5 mm3, 1‐month FU mean score: 416.1 ± 218.1 mm3, 12‐month FU mean sore: 431.2 ± 253.6 mm3, P = <0.0001, respectively) and penetration depth of keloids (relative reduction between baseline and 12‐month FU of 74.4%, P = <0.0001). The POSAS and DLQI scales confirmed significant objective and subjective improvements in scar appearance in all categories. The life quality associated with keloid appearance improved from a ‘moderate effect’ to a ‘small effect’ throughout the course of the study. Conclusions Results of this study confirm the efficacy and safety of the combination of 5‐FU and TAC in keloids. Treatments were well tolerated and demonstrated stable results at 12‐month FU

Imaging of cardiac neuronal function after cocaine exposure using Carbon-11 hydroxyephedrine and positron emission tomography

AbstractObjectives. The aim of the study was to define the effect of cocaine on the myocardial uptake and retention of C-11 hydroxyephedrine in the anesthetized dog model.Background. Cardiac toxcity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by the sympathetic nerve terminals of the heart. Carbon-11 hydroxyephedrine is a C-11-labled norepinephrine analog that has high specific affinity for uptake-1 and thus makes possible the assessment of the effect of cocaine on norepinephrine reuptake by cardiac sympathetic nerve terminals.Methods. The cardiac kinetics of C-11 hydroxyephedrine as assessed by dynamic positron emission tomographic imaging were used to characterize norepinephrine reuptake by the sympathetic nerve terminals. Carbon-11 hydroxyephedrine was injected intravenously before, as well as at 5 min and 2.5 h after, intravenous administration of 2 mg/kg body weight of cocaine in anesthetized dogs. Hemodynamic variables and microsphere-determined cardiac blood flow were also measured before and after cocaine exposure.Results. Intravenous injection of cocaine did not significantly affect hemodynamic variables and myocardial blood flow in the anesthetized animals. Compared with baseline, myocardial retention of C-11 hydroxyephedrine was significantly reduced by 78 ± 3% (mean ± SD) at 5 min and remained significantly reduced (28 ± 17%) at 2.5 h after cocaine injection. Cocaine administration after C-11 hydroxyephedrine injection (39 min) resulted in rapid biexponential clearance of C-11 hydroxyephedrine from myocardium.Conclusions. These results suggest prolonged effects of cocaine on the sympathetic nerve terminals of the heart. Positron emission tomography provides a noninvasive and sensitive means to objectively assess the cardiac pharmacokinetics of drugs such as cocaine

Horizons in Coupling of Sulfur-Bearing Silanes to Hydrothermally Treated Lignin toward Sustainable Development

The development of hydrothermally treated (HTT) lignin as a promising reinforcing filler for elastomers is challenged by the use of different sulfur-bearing silane coupling agents. Though the application of certain sulfur silane-modified HTT lignin, in particular bis(3-triethoxysilylpropyl)tetrasulfide, improves the in-rubber properties relative to the unmodified and other sulfur silane-modified ones, it results in the formation of distinctive spongelike filler textures within the rubber matrix, as observed by atomic force microscopy. It is of prime importance to understand the reason behind this formation of emerging filler cluster units and the less reinforcing efficiency of other sulfur silane-modified ones. This demanded the elucidation of the coupling reaction of hydrothermally treated lignin and sulfur silane modifiers as it can widen the application window for hydrothermally treated lignin in rubber technology and facilitate the use of these renewable materials. To gain insight into this phenomenon, HTT lignin and their model compounds were subjected to modifications using coupling agents bearing the specific silane functionalities, alkoxy and thiol. By detailed nuclear magnetic resonance investigations, it is shown that the underlying principle of coupling occurs between the thiols of silane and lignin. This systematic study also exemplifies that the ethoxy and/or the silanol groups of silane are unreactive toward the lignin surface and are only capable of self-condensation. In summary, a different coupling phenomenon is observed for hydrothermally treated lignin and sulfur silane, explaining both the cluster formation and the obtained reinforcing properties.</p

Diagnostic Value of Contrast-Enhanced Magnetic Resonance Imaging and Single-Photon Emission Computed Tomography for Detection of Myocardial Necrosis Early After Acute Myocardial Infarction

ObjectivesThis study sought to evaluate the diagnostic value of contrast-enhanced magnetic resonance imaging (CMR) and single-photon emission computed tomography (SPECT) for detection of myocardial necrosis after acute myocardial infarction (AMI).BackgroundSingle-photon emission computed tomography is widely accepted in the clinical setting for detection and estimation of myocardial infarction. Contrast-enhanced magnetic resonance imaging offers technical advantages and is therefore a promising new method for identification of infarcted tissue.MethodsSeventy-eight patients with AMI were examined by CMR and SPECT 7 days after percutaneous coronary intervention. Contrast-enhanced magnetic resonance imaging and SPECT images were scored for presence and location of infarction using a 17-segment model. Results were compared with the peak troponin T level, electrocardiographic, and angiographic findings.ResultsAcute myocardial infarction was detected significantly more often by CMR than SPECT (overall sensitivity: 97% vs. 87%; p = 0.008). Sensitivity of CMR was superior to SPECT in detecting small infarction as assessed by the peak troponin T level <3.0 ng/ml (92 vs. 69%; p = 0.03), and infarction in non-anterior location (98% vs. 84%; p = 0.03). Non–Q-wave infarctions were more likely to be detected by CMR (sensitivity 85% vs. 46%; p = 0.06). While CMR offered high sensitivity for detection of AMI irrespective of the infarct-related artery, SPECT was less sensitive, particularly within the left circumflex artery territory.ConclusionsContrast-enhanced magnetic resonance imaging is superior to SPECT in detecting myocardial necrosis after reperfused AMI because CMR detects small infarcts that were missed by SPECT independent of the infarct location. Thus, CMR is attractive for accurate detection and assessment of the myocardial infarct region in patients early after AMI

Modelling the unfolding pathway of biomolecules: theoretical approach and experimental prospect

We analyse the unfolding pathway of biomolecules comprising several independent modules in pulling experiments. In a recently proposed model, a critical velocity $v_{c}$ has been predicted, such that for pulling speeds $v>v_{c}$ it is the module at the pulled end that opens first, whereas for $v<v_{c}$ it is the weakest. Here, we introduce a variant of the model that is closer to the experimental setup, and discuss the robustness of the emergence of the critical velocity and of its dependence on the model parameters. We also propose a possible experiment to test the theoretical predictions of the model, which seems feasible with state-of-art molecular engineering techniques.Comment: Accepted contribution for the Springer Book "Coupled Mathematical Models for Physical and Biological Nanoscale Systems and Their Applications" (proceedings of the BIRS CMM16 Workshop held in Banff, Canada, August 2016), 16 pages, 6 figure

Positron emission tomography detects evidence of viability in rest technetium-99m sestamibi defects

AbstractObjectives. The purpose of this study was to determine the relative value of single-photon emission computed tomographic (SPECT) imaging at rest using technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi) with positron emission tomography for detection of viable myocardium.Background. Recent studies comparing positron emission tomography and thallium-201 reinjection with rest technetium-99m sestamibi imaging have suggested that the latter technique underestimates myocardial viability.Methods. Twenty patients with a previous myocardial infarction underwent rest technetium-99m sestamibi imaging and positron emission tomography using fluorine (F)-18 deoxyglucose and nitrogen (N)-13 ammonia. In each patient, circumferential profile analysis was used to determine technetium-99m sestamibi, F-18 deoxyglucose and N-13 ammonia activity (expressed as percent of peak activity) in nine cardiac segments and in the perfusion defect defined by the area having technetium-99m sestamibi activity <60%. Technetium-99m sestamibi defects were graded as moderate (50% to 59% of peak activity) and severe (<50% of peak activity). Estimates of perfusion defect size were compared between technetium-99m sestamibi and N-13 ammonia.Results. Sixteen (53%) of 30 segments with moderate defects and 16 (47%) of 34 segments with severe defects had ≥60% F-18 deoxyglocose activity considered indicative of viability. Fluorine-18 deoxyglucose evidence of viability was still present in 50% of segments with technetium-99m sestamibi activity <40%. There was no significant difference in the mean (± SD) technetium-99m sestamibi activity in segments with viable (40 ± 7%) and nonviable segments (49 ± 7%, p = 0.84). Of the 18 patients who had adequate F-18 deoxyglucose studies, the area of the technetium-99m sestamibi defect was viable in 5 (28%). In 16 patients (80%), perfusion defect size determined by technetium-99m sestamibi exceeded that measured by N-13 ammonia. The difference in defect size between technetium-99m sestamibi and N-13 ammonia was significantly greater in patients with viable (21 ± 9%) versus nonviable segments (7 ± 9%, p = 0.007).Conclusions. Moderate and severe rest technetium-99m sestamibi defects frequently have metabolic evidence of viability. Technetium-99m sestamibi SPECT yields larger perfusion defects than does N-13 ammonia positron emission tomography when the same threshold values are used

Hail formation triggers rapid ash aggregation in volcanic plumes.

During explosive eruptions, airborne particles collide and stick together, accelerating the fallout of volcanic ash and climate-forcing aerosols. This aggregation process remains a major source of uncertainty both in ash dispersal forecasting and interpretation of eruptions from the geological record. Here we illuminate the mechanisms and timescales of particle aggregation from a well-characterized 'wet' eruption. The 2009 eruption of Redoubt Volcano, Alaska, incorporated water from the surface (in this case, a glacier), which is a common occurrence during explosive volcanism worldwide. Observations from C-band weather radar, fall deposits and numerical modelling demonstrate that hail-forming processes in the eruption plume triggered aggregation of ∼95% of the fine ash and stripped much of the erupted mass out of the atmosphere within 30 min. Based on these findings, we propose a mechanism of hail-like ash aggregation that contributes to the anomalously rapid fallout of fine ash and occurrence of concentrically layered aggregates in volcanic deposits.AVE acknowledges NSF Postdoctoral Fellowship EAR1250029 and a seed grant from NASA Ames Supercomputing Center. Integrated Data Viewer (IDV) software from UCAR/Unidata was used in the analysis and visualization of the large-eddy simulation. ASTER GDEM is a product of NASA and METI. NCAR Reanalysis data provided by the NOAA/OAR/ESRL Physical Sciences Division, Boulder, Colorado, USA. We acknowledge Victoria University of Wellington, New Zealand, for access to the laser particle size analyzer, and Matt Rogers at University of Alaska, Anchorage for use of the freeze dryer. Rick Hoblitt is thanked for discussions and comments on the manuscript.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms886