bluuebunny/crossref_metadata_2025 huggingface dataset:
A RXR Ligand 6-OH-11-O-Hydroxyphenanthrene with Antitumour Properties Enhances (−)-Epigallocatechin-3-gallate Activity in Three Human Breast Carcinoma Cell Lines
Authors: Farabegoli Fulvia , Govoni Marzia , Ciavarella Carmen , Orlandi Marina , Papi Alessio
Published: June 2014

(−)-Epigallocatechin-3-gallate (EGCG) and chemotherapeutic agents cotreatment can improve cytotoxicity against cancer cells. We showed that EGCG and the rexinoid 6-OH-11-O-hydroxyphenanthrene (IIF), given together, were cytotoxic toward MCF-7, MCF-7TAM, and MDA-MB-231, three breast carcinoma cell lines showing different molecular characteristics. Cell growth arrest and apoptosis were greater after EGCG and IIF cotreatment than after individual administration. Cytotoxicity was related to upregulation of 67-kDa laminin receptor (LR67), one of the principal molecular targets of EGCG, and activation of the nuclear retinoic X receptors (RXRs) pathway. Furthermore, the transcription factor Forkhead box O3 (Foxo3a), a protein able to trigger apoptosis through upregulation of genes necessary for cell death, was activated. EGCG and IIF cotreatment produced a significant nuclear import of Foxo3a from the cytoplasm in MCF-7, MCF-7TAM, and MDA-MB-231 cells. In MCF-7TAM cells only, Foxo3a nuclear localization was associated with p473AKT downregulation. For the first time we showed that when EGCG and IIF, two harmless molecules, were given together, they might increase cytotoxicity in three breast carcinoma cell lines, two of them being representative of poorly responsive breast carcinoma types.
Gradient Based Adaptive Algorithm for Echo Cancellation from Recorded Echo Corrupted Speech
Authors: Mahbub Upal , Fattah Shaikh Anowarul
Published: June 2014

An offline single channel acoustic echo cancellation (AEC) scheme is proposed based on gradient based adaptive least mean squares (LMS) algorithm considering a major practical application of echo cancellation system for enhancing recorded echo corrupted speech data. The unavailability of a reference signal makes the problem of single channel adaptive echo cancellation to be extremely difficult to handle. Moreover, continuous feedback of the echo corrupted signal to the input microphone can significantly degrade the quality of the original speech signal and may even result in howling. In order to overcome these problems, in the proposed scheme, the delayed version of the echo corrupted speech signal is considered as a reference. An objective function is thus formulated and thereby a modified LMS update equation is derived, which is shown to converge to the optimum Wiener-Hopf solution. The performance of the proposed method is evaluated in terms of both subjective and objective measures via extensive experimentation on several real-life echo corrupted signals and very satisfactory performance is obtained.
Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide‐Induced Acute Lung Injury in Mice
Authors: Chu Chun-jun , Xu Nai-yu , Li Xian-lun , Xia Long , Zhang Jian , Liang Zhi-tao , Zhao Zhong-zhen , Chen Dao-feng
Published: June 2014

Rabdosia japonica var. glaucocalyx (Maxim.) Hara, belonging to the Labiatae family, is widely used as an anti‐inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim.) Hara (RJFs) in acute lung injury (ALI) mice induced by lipopolysaccharide (LPS). Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg) per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3) in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS‐induced ALI via reducing productions of the level of inflammatory mediators (TNF‐α, IL‐6, and IL‐1β), and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO) activity and nitric oxide (NO) and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS‐induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.
Analytical Solution for MHD Flow of a Magnetic Fluid within a Thick Porous Annulus
Authors: Yeh Shihhao , Chen Tsai-Jung , Leong Jik Chang
Published: June 2014

The steady-state problem of a magnetic fluid filling a porous annulus between two cylindrical walls under the influence of a nonuniform radially outward magnetic field has been investigated. The cylindrical walls are either electrically perfectly insulated or electrically perfectly conducting. The permeability of the porous annulus increases with its radial location. The governing partial differential equations were derived carefully and closed form solutions for the profiles of the velocity component and the induced magnetic component were obtained. The effect of the strength of the externally applied magnetic field, the permeability of the porous annulus, and the conductivity of the cylindrical walls were examined through the angular velocity components, as well as the induced magnetic field.
Successful Advanced Maternal Age Pregnancy with Mosaic Turner Syndrome Conceived after Ovulation Induction with Clomiphene Citrate: A Case Report
Authors: Murakami Masahiro , Hinokio Kenji , Kiyokawa Machiko , Morine Mikio , Iwasa Takeshi
Published: June 2014

Turner women typically experience gonadal dysfunction that results in amenorrhea and sterility. We encountered a case of mosaic Turner syndrome where conception was possible after ovulation induction with clomiphene citrate (CC). The patient’s ovaries were overresponsive to induction with CC. The challenges and successful outcome are reported.
Comparison of Maxillary Molar Distalization with an Implant-Supported Distal Jet and a Traditional Tooth-Supported Distal Jet Appliance
Authors: Cozzani Mauro , Pasini Marco , Zallio Francesco , Ritucci Robert , Mutinelli Sabrina , Mazzotta Laura , Giuca Maria Rita , Piras Vincenzo
Published: June 2014

Aim. To investigate and compare the efficiency of two appliances for molar distalization: the bone-anchored distal screw (DS) and the traditional tooth-supported distal jet (DJ) for molar distalization and anchorage loss.Methods.Tests (18 subjects) were treated with a DS and controls (18 subjects) were treated with a DJ. Lateral cephalograms were obtained before and at the end of molar distalization and were analysed. Shapiro Wilk test, unpairedt-test, and Wilcoxon rank-sum test were applied according to values distribution. Theαlevel was fixed at 0.05.Results. Maxillary first molars were successfully distalized into a Class I relationship in all patients. The mean molar distalization and treatment time were similar in both groups. The DS group exhibited a spontaneous distalization (2.1±0.9 mm) of the first premolar with control of anchorage loss, distal tipping, extrusion, and skeletal changes.Conclusions. The DS is an adequate compliance-free distalizing appliance that can be used safely for the correction of Class II malocclusions. In comparison to the traditional DJ, the DS enables not only a good rate of molar distalization, but also a spontaneous distalization of the first premolars.
Directly-Observed Intermittent Therapy versus Unsupervised Daily Regimen during the Intensive Phase of Antituberculosis Therapy in HIV Infected Patients
Authors: Alvarez-Uria Gerardo , Midde Manoranjan , Pakam Raghavakalyan , Naik Praveen Kumar
Published: June 2014

The World Health Organization strongly recommends using daily antituberculosis therapy (ATT) during the intensive phase for HIV infected patients. India has the highest burden of tuberculosis in the world, but HIV infected patients are still receiving intermittent ATT. In this study we compared the mortality in patients who received directly-observed intermittent ATT versus self-administered daily ATT with fixed dose combinations during the intensive phase in a context of freely available antiretroviral therapy. The study included 1460 patients, 343 in the intermittent ATT group and 1117 in the daily ATT group. Baseline covariates of the two groups were balanced using inverse probability of treatment weighting based on propensity score methods. In a sensitivity analysis, continuous variables (albumin, CD4 count, and age) were modelled using restricted cubic smoothing splines. Compared with patients who received daily ATT, patients who received intermittent ATT had a 40% higher risk of mortality (1.4 hazard ratio; 95% confidence interval, 1.14–1.7). We estimated that the use of daily ATT could achieve a 10% absolute reduction in mortality at 12 months. Self-administered daily ATT was not associated with an increased risk of default from treatment. These results support the immediate implementation of daily ATT for HIV infected patients during the intensive phase in India.
Optimization of Two-Step Acid-Catalyzed Hydrolysis of Oil Palm Empty Fruit Bunch for High Sugar Concentration in Hydrolysate
Authors: Zhang Dongxu , Ong Yee Ling , Li Zhi , Wu Jin Chuan
Published: June 2014

Getting high sugar concentrations in lignocellulosic biomass hydrolysate with reasonable yields of sugars is commercially attractive but very challenging. Two-step acid-catalyzed hydrolysis of oil palm empty fruit bunch (EFB) was conducted to get high sugar concentrations in the hydrolysate. The biphasic kinetic model was used to guide the optimization of the first step dilute acid-catalyzed hydrolysis of EFB. A total sugar concentration of 83.0 g/L with a xylose concentration of 69.5 g/L and a xylose yield of 84.0% was experimentally achieved, which is in well agreement with the model predictions under optimal conditions (3% H2SO4and 1.2% H3PO4, w/v, liquid to solid ratio 3 mL/g, 130°C, and 36 min). To further increase total sugar and xylose concentrations in hydrolysate, a second step hydrolysis was performed by adding fresh EFB to the hydrolysate at 130°C for 30 min, giving a total sugar concentration of 114.4 g/L with a xylose concentration of 93.5 g/L and a xylose yield of 56.5%. To the best of our knowledge, the total sugar and xylose concentrations are the highest among those ever reported for acid-catalyzed hydrolysis of lignocellulose.
Prediction of Rain Attenuation and Impact of Rain in Wave Propagation at Microwave Frequency for Tropical Region (Uttarakhand, India)
Authors: Kestwal Mukesh Chandra , Joshi Sumit , Garia Lalit Singh
Published: June 2014

The most classical approach of determining rain attenuation for radio-wave frequency has been to theoretically determine the specific attenuation. At frequency over 10 GHz, rain and precipitation can influence the attenuation a lot; the effect of atmospheric attenuation between the source and destination over wireless communication is of major concern and a proper site visit and proper method are required to control the attenuation level so that the performance can be increased. In this paper exponential model has been used to determine the attenuation level for k-region (India) which can be used for region having similar condition. The analyzed predicted attenuation data have been compared with ITU-R measured rain attenuation, and the results will provide useful estimation of rainfall attenuation on microwave links in tropical regions that have similar conditions as (Almora) Uttarakhand region.
Effects of Irrigation with Treated Wastewater on Root and Fruit Mineral Elements of Chemlali Olive Cultivar
Authors: Bedbabis Saida , Ben Rouina Béchir , Boukhris Makki , Ferrara Giuseppe
Published: June 2014

Twenty-year-old “Chemlali” olive trees trained to vase and rainfed were investigated in either “on” (2004) or “off” (2003) year. A randomized block design with three blocks and three treatments was used and each experimental plot consisted of nine olive trees. Three treatments were applied: (1) rainfed conditions (RF, used as control treatment); (2) irrigation with well water (WW); and (3) irrigation with treated wastewater (TWW). Irrigation with TWW led to a significant increase of root N, P, Ca, Zn, Mn, Na, and Cl concentrations, in particular in the on-year. Data showed significant differences, between the two years, for the concentration of the mineral elements in the roots, with general lower values in the on-year, probably as a consequence of nutrients movement upward in the tree. Fruit N, P, K, Zn, Mn, and Cl contents were significantly higher in TWW irrigated trees with respect to both RF and WW trees, whereas similar values for Ca, Mg, Na, and Cl contents were measured for WW and TWW irrigated trees. The irrigation with TWW allowed to reuse problematic waters and to save nutrients inputs in the olive orchard thus moving towards a more sustainable management of olive orchards in countries where water is the major limiting factor for agriculture.
Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in Patients with Breast Cancer
Authors: Rodriguez-Gil Jorge L. , Takita Cristiane , Wright Jean , Reis Isildinha M. , Zhao Wei , Lally Brian E. , Hu Jennifer J.
Published: June 2014

Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Postsurgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASR) that impact quality of life and treatment outcomes.

Methods: We evaluated an inflammatory biomarker, C-reactive protein (CRP), in predicting RT-induced EASRs in 159 patients with breast cancer undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Associations between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders.

Results: RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, a significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP > 1 mg/L [odds ratio (OR), 2.51; 95% confidence interval (CI), 1.06–5.95; P = 0.04], obesity (OR, 2.08; 95% CI, 1.03–4.21; P = 0.04), or combined both factors (OR, 5.21; 95% CI, 1.77–15.38; P = 0.003).

Conclusion: This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity.

Impact: Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in patients with breast cancer undergoing RT. Cancer Epidemiol Biomarkers Prev; 23(9); 1873–83. ©2014 AACR.
Differences in the Transcriptional Response to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer
Authors: Patani Neill , Dunbier Anita K. , Anderson Helen , Ghazoui Zara , Ribas Ricardo , Anderson Elizabeth , Gao Qiong , A'hern Roger , Mackay Alan , Lindemann Justin , Wellings Robert , Walker Jill , Kuter Irene , Martin Lesley-Ann , Dowsett Mitch
Published: June 2014

Purpose: Endocrine therapies include aromatase inhibitors and the selective estrogen receptor (ER) downregulator fulvestrant. This study aimed to determine whether the reported efficacy of fulvestrant over anastrozole, and high- over low-dose fulvestrant, reflect distinct transcriptional responses.

Experimental Design: Global gene expression profiles from ERα-positive breast carcinomas before and during presurgical treatment with fulvestrant (n = 22) or anastrozole (n = 81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and estrogen deprivation were identified and integrated using Gene Ontology, pathway and network analyses to evaluate their potential significance.

Results: The overall transcriptional response to fulvestrant and estrogen deprivation was correlated (r = 0.61 in presurgical studies, r = 0.87 in vitro), involving downregulation of estrogen-regulated and proliferation-associated genes. The transcriptional response to fulvestrant was of greater magnitude than estrogen deprivation (slope = 0.62 in presurgical studies, slope = 0.63 in vitro). Comparative analyses identified 28 genes and 40 Gene Ontology categories affected differentially by fulvestrant. Seventeen fulvestrant-specific genes, including CAV1/2, SNAI2, and NRP1, associated with ERα, androgen receptor (AR), and TP53, in a network regulating cell cycle, death, survival, and tumor morphology. Eighteen genes responding differently to fulvestrant specifically predicted antiproliferative response to fulvestrant, but not anastrozole. Transcriptional effects of low-dose fulvestrant correlated with high-dose treatment, but were of lower magnitude (ratio = 0.29).

Conclusions: The transcriptional response to fulvestrant has much in common with estrogen deprivation, but is stronger with distinctions potentially attributable to arrest of estrogen-independent ERα activity and involvement of AR signaling. Genes responding differently to fulvestrant may have predictive utility. These data are consistent with the clinical efficacy of fulvestrant versus anastrozole and higher dosing regimens. Clin Cancer Res; 20(15); 3962–73. ©2014 AACR.
TP53 Mutations and Lung Cancer: Not All Mutations Are Created Equal
Authors: Govindan Ramaswamy , Weber Jason
Published: June 2014

Mutations in TP53 are common in non–small cell lung cancer. Apart from the loss of tumor-suppressor functions, TP53 mutations may result in gain of function favoring cellular proliferation, inhibition of apoptosis, and genomic instability. Some TP53 mutations are more likely to affect the course of the disease than others. Clin Cancer Res; 20(17); 4419–21. ©2014 AACR.
EZH2 Represses Target Genes through H3K27-Dependent and H3K27-Independent Mechanisms in Hepatocellular Carcinoma
Authors: Gao Shu-Bin , Zheng Qi-Fan , Xu Bin , Pan Chang-Bao , Li Kang-Li , Zhao Yue , Zheng Qi-Lin , Lin Xiao , Xue Li-Xiang , Jin Guang-Hui
Published: June 2014

Alterations of polycomb group (PcG) genes directly modulate the trimethylation of histone H3 lysine 27 (H3K27me3) and may thus affect the epigenome of hepatocellular carcinoma (HCC), which is crucial for controlling the HCC cell phenotype. However, the extent of downstream regulation by PcGs in HCC is not well defined. Using cDNA microarray analysis, we found that the target gene network of PcGs contains well-established genes, such as cyclin-dependent kinase inhibitors (CDKN2A), and genes that were previously undescribed for their regulation by PcG, including E2F1, NOTCH2, and TP53. Using chromatin immunoprecipitation assays, we demonstrated that EZH2 occupancy coincides with H3K27me3 at E2F1 and NOTCH2 promoters. Interestingly, PcG repress the expression of the typical tumor suppressor TP53 in human HCC cells, and an increased level of PcG was correlated with the downregulation of TP53 in certain HCC specimens. Unexpectedly, we did not find obvious H3K27me3 modification or an EZH2 binding signal at the TP53 promoters, suggesting that PcG regulates TP53 expression in an H3K27me3-independent manner. Finally, the reduced expression of PcGs effectively blocked the aggressive signature of liver cancer cells in vitro and in vivo.

Implications: Taken together, our results establish the functional and mechanistic significance of certain gene regulatory networks that are regulated by PcGs in HCC.

Visual Overview: http://mcr.aacrjournals.org/content/12/10/1388/F1.large.jpg.

Mol Cancer Res; 12(10); 1388–97. ©2014 AACR.
The Future of Ischemic Stroke: Flow from Prehospital Neuroprotection to Definitive Reperfusion
Authors: Ip Hing Lung , Liebeskind David S.
Published: June 2014

Recent advances in ischemic stroke enable a seamless transition of the patient flow from the prehospital setting to definitive reperfusion, without the arbitrary separation of therapeutic phases of ischemia based on time alone. In 2013, the framework to understand and directly address the pathophysiology of cerebral blood flow that determines the timeline or evolution of ischemia in an individual case is given. This continuum of flow and the homeostasis of brain perfusion balanced by collaterals may be captured with serial imaging. Ongoing imaging core laboratory activities permit large-scale measurement of angiographic and tissue biomarkers of ischemia. Prehospital neuroprotection has become a reality and may be combined with revascularization therapies. Recent studies confirm that image-guided thrombolysis may be achieved without restrictive time windows. Baseline imaging patterns may be used to predict response to therapy and serial imaging may discern recanalization and reperfusion. Advanced techniques, such as arterial spin-labeled MRI, may also report hyperperfusion associated with hemorrhagic transformation. Endovascular therapies, including novel stent retriever devices, may augment revascularization and angiographic core laboratories may define optimal reperfusion. Serial evaluation of collaterals and reperfusion may identify definitive reperfusion linked with good clinical outcome rather than imposing arbitrary definitions of effective recanalization. Reperfusion injury and hemorrhagic transformation of various types may be detailed to explain clinical outcomes. Similar approaches may be used in intracranial atherosclerosis where flow, and not the degree of luminal stenosis, is paramount. Fractional flow may now be measured with computational fluid dynamics to identify high-risk lesions that require revascularization to restore the equilibrium of antegrade and collateral perfusion. Serial perfusion imaging of such cases may also illustrate inadequate cerebral blood volume gradients that may be more informative than blood flow delay alone. In sum, the growing understanding of collateral perfusion throughout all stages of ischemic stroke provides a framework for the future of ischemic stroke.
Carotid Baroreceptor Stimulation: A Potential Solution for Resistant Hypertension
Authors: Zhang Jun , Zhou Shuyu , Xu Gelin
Published: June 2014

Resistant hypertension indicates that the blood pressure cannot reach the target value despite standard drug treatment, which harbors an increased risk for cardiovascular diseases. The role of the carotid sinus in regulating blood pressure has long been observed; thereby, the idea that treating resistant hypertension by stimulating carotid baroreceptors emerged. Nevertheless, this idea has been abandoned for years due to technical limitations. Recently, with the evolutions in implantable electrical devices, expectations for treating resistant hypertension with baroreceptor stimulation have increased. Positive results from several multicenter clinical trials further captured the researchers' enthusiasm for more effective baroreceptor-stimulating devices. This study reviews the recent progress in baroreceptor stimulation as a treatment alternative for resistant hypertension.
Understanding Swiss Drug Policy Change and the Introduction of Heroin Maintenance Treatment
Authors: Khan Riaz , Khazaal Yasser , Thorens Gabriel , Zullino Daniele , Uchtenhagen Ambros
Published: June 2014

Aims: The aim of this paper is to illustrate how Switzerland was able to play such a pioneering role in the field of addiction treatment, in creating a drug policy that includes the medical prescription of diacetylmorphine (heroin). The paper will also describe the role of knowledge brokering processes and coalition building in the different phases of the development of the Swiss drug policy. Discussion: The medical prescription of diacetylmorphine was the exotic element of the Swiss drug policy of 1991 and probably still is one of the most controversial practices in clinical medicine despite its documented effectiveness. Coalitions of change actors, across stakeholder groups from many professions and politicians on various levels, succeeded in formulating and starting initiatives for a new drug policy and its innovations. Clear, shared objectives and a common feeling of urgency brought the coalitions together. Conclusion: In the case of Switzerland, the Confederation took a leading role by facilitating communication, encouraging scientific knowledge and bringing the various stakeholders on a platform to deliver a consensual political policymaking basis. This was facilitated by the Swiss direct democracy system. Sustained dialogue between researchers and the users of research enhances the likelihood of research affecting policy.
The Effects of Neurotrophins and the Neuropeptides VIP and PACAP on HIV-1 Infection: Histories with Opposite Ends
Authors: Souza Thiago Moreno L. , Temerozo Jairo R. , Giestal-de-Araujo Elizabeth , Bou-Habib Dumith Chequer
Published: June 2014

The nerve growth factor (NGF) and other neurotrophins, and the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are largely present in human tissue and can exert modulatory activities on nervous, endocrine and immune system functions. NGF, VIP and PACAP receptors are expressed systemically in organisms, and thus these mediators exhibit pleiotropic natures. The human immunodeficiency virus type 1 (HIV-1), the causal agent of the acquired immunodeficiency syndrome (AIDS), infects immune cells, and its replication is modulated by a number of endogenous factors that interact with HIV-1-infected cells. NGF, VIP and PACAP can also affect HIV-1 virus particle production upon binding to their receptors on the membranes of infected cells, which triggers cell signaling pathways that modify the HIV-1 replicative cycle. These molecules exert opposite effects on HIV-1 replication, as NGF and other neurotrophins enhance and VIP and PACAP reduce viral production in HIV-1-infected human primary macrophages. The understanding of AIDS pathogenesis should consider the mechanisms by which the replication of HIV-1, a pathogen that causes chronic morbidity, is influenced by neurotrophins, VIP and PACAP, i.e. molecules that exert a broad spectrum of physiological activities on the neuroimmunoendocrine axis. In this review, we will present the main effects of these two groups of mediators on the HIV-1 replicative cycle, as well as the mechanisms that underlie their abilities to modulate HIV-1 production in infected immune cells, and discuss the possible repercussion of the cross talk between NGF and both neuropeptides on the pathogenesis of HIV-1 infection.
Stenting and Angioplasty of Small Cerebral Arteries in Symptomatic Intracranial Atherosclerotic Disease
Authors: Zaidat Osama O. , Kalia Junaid , Nourollah-Zadeh Emad , Castonguay Alicia C. , Lazzaro Marc , Lynch John , Fitzsimmons Brian-Fred
Published: June 2014

Background: Intracranial atherosclerotic disease (ICAD) is a common cause of stroke with a poor natural history despite medical therapy. Few studies have investigated endovascular therapies for the treatment of symptomatic ICAD in distal intracranial arteries. Here, we present the feasibility and safety of balloon angioplasty with and without stenting in patients with medically refractory small-artery symptomatic ICAD. Methods: Personal logs were reviewed to identify patients who were treated for small-artery ICAD (stenosis >50%) using angioplasty and/or stenting. Small cerebral arteries were defined by a diameter of ≤2 mm or any branch distal to a large intracranial vessel (i.e. distal to the internal carotid artery, M1, A1, or vertebrobasilar trunk). Patient characteristics, clinical manifestations, treatment, hospital course, and follow-up data were collected and analyzed. Results: Ten patients (12 arteries) were treated with either primary balloon angioplasty (58.3%) or angioplasty with stenting (41.6%) with a 100% technical success rate. Mean pretreatment stenosis was 79.9%, while mean posttreatment stenosis was 19.0%. There were no major periprocedural complications, including symptomatic intracranial hemorrhage or mortality; 3 cases were complicated by groin hematoma. Patients were followed for a mean total of 18.6 months with only 1 symptomatic restenosis which was retreated successfully. All patients had good functional outcome with a modified Rankin Scale of either 0 (80%) or 1 (20%) on follow-up. Conclusion: In our case series, treatment of symptomatic small-artery ICAD with angioplasty and/or stenting was safe and effective. These interventions should be considered as an alternative treatment for ICAD patients refractory to medical therapy.
Clinical Imaging Assessments of Knee Osteoarthritis in the Elderly: A Mini-Review
Authors: Wick Marius C. , Kastlunger Martin , Weiss Rüdiger J.
Published: June 2014

Knee osteoarthritis (OA) in the elderly is one of the most common degenerative age-related joint diseases leading to typical degradation of articular cartilage with severe pain and limitation of joint motion. Its increasing prevalence due to the demographic development of the society has major implications for individual and public healthcare with the increasing necessity for clinical imaging assessment in a high number of individuals. Although conventional X-ray radiographs are widely considered as gold standard for the assessment of knee OA, in clinical and scientific settings they increasingly bare significant limitations in situations when high resolution and detailed assessment of cartilage is demanded. New imaging modalities are broadening the possibilities in knee OA clinical practice and are offering new insights to help for a better understanding of the disease. X-ray analysis in OA of the knee is associated with many technical limitations and increasingly is replaced by high-quality assessment using magnetic resonance imaging or ultrasonography both in clinical routine and scientific situations. These novel imaging modalities enable an in vivo visualization of the quality of the cartilaginous structure and bone as well as all articular and periarticular tissues. Therefore, the limitations of radiographs in knee OA assessment could be overcome by these techniques. This review article should provide an insight into the most important radiological features of knee OA and their systematic visualization with different imaging approaches that can be used in clinical routine.
Implantable Left Ventricular Assist Devices and the Kidney
Authors: Mao Huijuan , Katz Nevin , Kim Jeong Chul , Day Sonya , Ronco Claudio
Published: June 2014

The use of left ventricular assist devices (LVADs) in treating patients with advanced heart failure restores cardiac output resulting in improved perfusion to multiple organ systems with important clinical benefits. Renal pathophysiology during LVAD support remains an evolving, poorly understood, and potentially dynamic problem. Changes in renal function after LVAD placement have been investigated in multiple studies with contradictory results. Renal dysfunction is common prior to LVAD placement, which complicates postoperative clinical outcomes. The purpose of this review is to assess the latest information regarding the effects of LVADs on renal function with regard to hemodynamics, physiology, pathology and clinical issues prior to and after placement of the devices. The review should then aid in identifying patients best suited to benefit from this technology and to refine the therapy to reduce associated risks.
Vitamin D and Pre-Eclampsia: Original Data, Systematic Review and Meta-Analysis
Authors: Hyppönen Elina , Cavadino Alana , Williams David , Fraser Abigail , Vereczkey Attila , Fraser William D. , Bánhidy Ferenc , Lawlor Deborah , Czeizel Andrew E.
Published: June 2014

Background/Aims: Vitamin D may protect from pre-eclampsia through influences on immune modulation and vascular function. To evaluate the role of vitamin D in the development of pre-eclampsia, we conducted a systematic review and meta-analysis including novel data from 2 large-scale epidemiological studies. Methods: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for prospective observational studies of association between vitamin D supplementation or status (measured by maternal 25-hydroxyvitamin D, 25(OH)D) with a subsequent risk of pre-eclampsia, or randomised controlled trials using vitamin D supplementation to prevent pre-eclampsia. The Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) and the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in meta-analyses with published studies. Results: Mothers receiving vitamin D supplementation earlier in pregnancy had lower odds of pre-eclampsia [pooled odds ratios (OR) 0.81 and 95% confidence interval (CI) 0.75-0.87, p = 2.4 × 10-8, 2 studies] in the meta-analysis of published studies with HCCSCA. The meta-analysis of published studies with ALSPAC suggested an association between higher serum 25(OH)D levels and a reduced risk of pre-eclampsia (pooled OR 0.52 and 95% CI 0.30-0.89, p = 0.02, 6 studies). Randomised trials of supplementation were suggestive of protective association (pooled OR 0.66 and 95% CI 0.52-0.83, p = 0.001, 4 studies). Conclusions: This study suggests that low maternal serum 25(OH)D concentrations increase pre-eclampsia risk and that vitamin D supplementation lowers this risk. The quality of evidence is insufficient to determine a causal association, which highlights the need for adequately powered clinical trials.
CT Urography for the Diagnosis of Medullary Sponge Kidney
Authors: Koraishy Farrukh M. , Ngo Thuy-Trang T. , Israel Gary M. , Dahl Neera K.
Published: June 2014

Background: Medullary sponge kidney (MSK) is characterized by malformation of the terminal collecting ducts and is associated with an increased risk of nephrolithiasis, nephrocalcinosis, urinary tract infections, renal acidification defects, and reduced bone density. It has been historically diagnosed with intravenous pyelography (IVP), which is falling out of favor as an imaging modality. CT urography (CTU) performed with multidetector CT (MDCT) has been shown to create images of the renal collecting system with similar detail as IVP; however, its utility in diagnosing MSK has not been defined. Case Report: We present the first 15 patients with recurrent symptomatic nephrolithiasis who were evaluated in our renal stone clinic with CTU. Four patients were diagnosed with MSK after visualization of the characteristic radiologic findings. Discussion: CTU effectively demonstrates the characteristic radiologic findings of MSK including collecting tubule dilatation, medullary nephrocalcinosis, nephrolithiasis, and medullary cysts. Dose reduction protocols can reduce radiation exposure below that associated with conventional IVP. We propose CTU be considered for the diagnosis of MSK.
Oligometastatic Breast Cancer: A Shift from Palliative to Potentially Curative Treatment?
Authors: Di Lascio Simona , Pagani Olivia
Published: June 2014

A distinctive subset of metastatic breast cancer is represented by the so called ‘oligometastatic' disease, characterized by single/few detectable metastatic lesions. A more aggressive multidisciplinary approach can be considered in this patient population: available data report favorable results of ‘radical' local therapy for limited metastatic disease at least in a subset of selected patients. Selection bias and the retrospective nature of data do not allow for generalization of the results: the use of such approaches must be individualized and managed within a multidisciplinary team of dedicated specialists. Improvement in surgical and radiation techniques, development of new tools to deliver local chemotherapy, and new procedures (i.e. cryosurgery, laser and microwave ablation) mandate careful evaluation of such single and combined modalities in controlled clinical trials. A more accurate identification of patients with limited metastases and better definition of treatment endpoints will also allow correct patient selection for locally aggressive therapies. This paper focusses on local treatment of the primary tumor and of the most frequent distant disease sites in the presence of oligometastatic disease.
Update on Rituximab: An Established Treatment for All Immune-Mediated Kidney Diseases?
Authors: Evans Rhys , Salama Alan D.
Published: June 2014

Rituximab, a monoclonal antibody directed against the CD20 antigen, found on certain B-cell subsets, results in significant B-cell depletion and has been increasingly used in immune-mediated renal disease and transplantation. Although originally applied to what were considered antibody-mediated diseases, it has become clear that auto- and alloreactive B cells contribute in many ways to immune dysfunction, and the benefit of B-cell depletion extends beyond reduction in auto- or alloantibody levels. Most positive data regarding the benefit of rituximab in immune-mediated kidney disease have come from uncontrolled cohort studies, with the only positive controlled clinical trials demonstrating efficacy for the treatment of systemic vasculitis. While negative trials may have potentially missed clinical effects due to trial design, there may be significant differences in responses in different diseases or lack of efficacy due to therapeutic overlap when used with certain drug combinations. Rituximab is a novel treatment that provides a clear alternative for patients in different clinical situations, and allows for customization of therapy. However, much remains to be understood as to how best to use it in a cost-effective manner, when not to use it, and what the long-term impact of therapy may be.
Nab-Paclitaxel for Metastatic Pancreatic Cancer: Clinical Outcomes and Potential Mechanisms of Action
Authors: Al-Batran Salah-Eddin , Geissler Michael , Seufferlein Thomas , Oettle Helmut
Published: June 2014

For almost 15 years there has been stagnation in the systemic treatment of patients with pancreatic ductal adenocarcinoma (PDAC). Recently, several developments seem to indicate clinically relevant improvements in the treatment of patients with metastatic disease. One of these developments is the introduction of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) into the firstline treatment of metastatic disease. In this review, underlying preclinical and clinical data are discussed, with a special focus on mechanisms of action, the potential interaction with albumin and calcium-binding matricellular glycoproteins, such as the secreted protein acidic and rich in cysteine (SPARC), as well as the clinical outcome associated with the use of nab-paclitaxel.
Placental Pathology in Early-Onset and Late-Onset Fetal Growth Restriction
Authors: Mifsud William , Sebire Neil J.
Published: June 2014

Several histopathological features are found more frequently in placentas from pregnancies complicated by fetal growth restriction (FGR), including villous infarction, maternal vascular changes and villous morphological alterations, although around one quarter of placentas associated with FGR lack any morphological abnormality on routine examination. Since similar changes may also affect clinically uncomplicated pregnancies, the positive predictive value of such findings for pathological FGR in an unselected case remains low. However, the pattern of placental pathologies varies with clinical subgroup. The combination of placental bed and parenchymal lesions in FGR with abnormal uterine artery Doppler velocimetry is essentially identical to preterm pre-eclampsia (PET), and there is an association between FGR with abnormal umbilical artery Doppler findings and lesions of fetal stem arteries and terminal villous hypovascularity. Conversely, placentas from pregnancies complicated by PET or FGR presenting at or near term have a significantly lower frequency of histological abnormalities compared to early-onset disease and absence of a distinctive biochemical profile. The histological placental findings in FGR are therefore varied, from morphologically unremarkable through to severe uteroplacental vasculopathy, with no single pathological feature associated with high sensitivity or specificity. Severe early-onset FGR, overlapping with severe early-onset PET, is mainly associated with features of impaired maternal uteroplacental perfusion secondary to defective extravillous trophoblast invasion, and its consequences. Late-onset FGR probably represents a more heterogeneous group with less characteristic histological changes. Future research using histopathological assessment of aggregated data from multiple studies into larger datasets with centralised pathology review will allow delineation of distinctive clinicopathological associations and further understanding of pathophysiology.
Dysphonia in Very Preterm Children: A Review of the Evidence
Authors: Reynolds Victoria , Meldrum Suzanne , Simmer Karen , Vijayasekaran Shyan , French Noel
Published: June 2014

Introduction: Intubation is a known risk factor for dysphonia yet is essential in the perinatal care of many very preterm infants. Children born preterm, who are frequently resuscitated with endotracheal intubation, may be at risk of dysphonia at school age and beyond. Objectives: To identify and describe the evidence pertaining to long-term voice outcomes and risk factors for developing dysphonia in preterm children. Results: In addition to case studies and series, three larger-scale studies have reported on dysphonia and voice outcomes in preterm children. Studies reporting treatment outcomes were not available. Factors associated with poor voice outcomes included female gender, birth weight <1,000 g, birth at <27 weeks' gestation, surgical closure of patent ductus arteriosus, emergency versus elective intubations and multiple intubations. Adverse voice outcomes were associated with laryngeal pathology and compensatory supraglottic compression. Conclusions: Dysphonia is a newly reported, long-term complication of preterm birth, yet the number of relevant studies remains limited. Further research is required to confirm the risk factors for developing dysphonia, which will inform future voice treatment studies.
The Efficacy of Fimasartan for Cardiovascular Events and Metabolic Syndrome (K-MetS Study): Rationale, Design and Participant Characteristics
Authors: Kim Changsoo , Kim Min Young , Kang Dae Ryong , Kim Jang-Young , Park Jeong Bae ,   on behalf of the K-MetS study investigators
Published: June 2014

Fimasartan, the eighth angiotensin receptor blocker, was launched in March 2011 and was found to have an excellent efficacy and safety profile in a large cross-sectional population study [Safety and Efficacy of Fimasartan in Patients with Arterial Hypertension (Safe-KanArb); Park et al.: Am J Cardiovasc Drugs 2013;13:47-56]. However, there is no long-term study to evaluate its efficacy for major adverse cardiovascular events (MACE) and other effects. The purpose of this study (K-MetS study) was to evaluate whether the early reduction of blood pressure (BP) and/or correction of metabolic derangements with fimasartan will affect MACE and the development of diabetes after long-term use in patients with hypertension. A total of 10,734 patients were screened between October 2011 and October 2012. Of these, 10,601 patients from 582 private clinics and 11 university hospitals were enrolled and are currently treated with fimasartan. The primary endpoints are MACE (cardiovascular mortality, stroke, myocardial infarction, and hospitalization for heart failure) and the development of diabetes after 3 years of follow-up. In addition to BP monitoring in the clinic, home BP monitoring is performed in about two thirds of patients. The patients were 56.2 ± 10.9 years old (mean ± SD), with 48.4% being women. The mean clinic and home systolic/diastolic BP at baseline were 145.0 ± 17.0/88.8 ± 11.4 and 138.6 ± 14.8/82.6 ± 9.9 mm Hg, respectively. The metabolic syndrome was found in 56.4%, increased abdominal circumference in 52.8%, elevated fasting glucose in 46.8%, hypertriglyceridemia in 44.7%, and low high-density lipoprotein cholesterol in 33.3% of patients. Further, complicated hypertension with diabetes occurred in 15.1%, ischemic heart disease in 3.3%, stroke in 0.9%, heart failure in 0.7%, and atrial fibrillation in 0.4% of patients. Most participants in this study had a low-to-moderate risk for hypertension. The K-MetS study is expected to provide valuable information about the effects of early BP control and correction of metabolic abnormalities on future cardiovascular outcomes relative to low-risk hypertension.
Pulse Pressure Is Useful for Determining the Choice of Antihypertensive Drugs in Postmenopausal Women
Authors: Suzuki Hiromichi
Published: June 2014

Objective: To assess the efficacy of various classes of antihypertensive drugs in postmenopausal women with hypertension using pulse pressure (PP) as an index. Patients and Methods: Selected women were required to be naturally menopausal for at least 1 year but not more than 5 years past their menstrual period. Exclusion criteria were a history of preeclampsia or eclampsia, a severe illness such as myocardial infarction or stroke within 6 months, the use of estrogens or progestins within 3 months, proteinuric nephropathy, and surgically induced menopause. There were 114 women who participated in this study after having given informed consent. These women were diagnosed as having hypertension based on an office blood pressure >140/90 mm Hg as well as a self-measured blood pressure at home >130/85 mm Hg. If both levels of blood pressure were not fulfilled, the patients were excluded. All antihypertensive medications were withdrawn 6 weeks before the initiation of the study. The patients were randomly assigned in equal numbers to the following groups: (1) combination therapy with losartan (angiotensin receptor blocker) 50 mg daily + trichlormethiazide (diuretic) 2 mg twice a week, and (2) combination therapy with cilnidipine (calcium channel blocker) 5 mg + arotinolol (αβ-blocker) 10 mg daily. Results: The patients were retrospectively divided into three groups according to their PP at the start of the study: Group I (n = 24), >65 mm Hg; Group II (n = 58), 65-45 mm Hg, and Group III (n = 32), <45 mm Hg. In Group I, combination therapy with cilnidipine + arotinolol resulted in a greater reduction in the systolic blood pressure than the combination therapy with losartan + trichlormethiazide (from 169/88 ± 2/5 to 133/73 ± 2/5 mm Hg vs. from 169/88 ± 2/5 to 149/66 ± 2/5 mm Hg, p < 0.05). On the other hand, in Group III, losartan + trichlormethiazide decreased diastolic as well as systolic blood pressures (from 152/106 ± 2/2 to 123/78 ± 1/1 mm Hg vs. from 149/107 ± 2/2 to 129/84 ± 2/1 mm Hg, p < 0.05). In Group II, there were no differences between the two antihypertensive regimens. Laboratory findings were not influenced by any type of treatment. Conclusions: PP measurement before starting medication for hypertension may be useful for determining the choice of antihypertensive drugs.
Wegener's Granulomatosis with an Atypical Presentation as Acute Tonsillitis
Authors: Arslan Selçuk , Işik Abdülcemal Ümit , Mungan Sevdegül , Ural Ahmet , Sarı Refik Ali
Published: June 2014

Wegener's granulomatosis (WG) is a rare necrotizing granulomatous vasculitis of unknown etiology commonly involving vessels, the upper and lower respiratory system and the kidneys. There are various symptoms and signs of WG due to a wide spectrum of involvement sites. The initial presentation of the disease as intraoral lesions is rare. In this paper, a case of WG that presented with a necrotic lesion confined to the right tonsil before other symptoms and signs occurred is described. The diagnosis was established based on the clinical presentation and the histopathological findings of the characteristic inflammatory pattern.