bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Conventional and Ultrasonic-Assisted Extraction on Phenolic Contents, Betacyanin Contents, and Antioxidant Capacity of Red Dragon Fruit (Hylocereus polyrhizus)
Authors: Ramli Nurul Shazini , Ismail Patimah , Rahmat Asmah
Published: October 2014

The aim of this study was to examine the effects of extraction methods on antioxidant capacities of red dragon fruit peel and flesh. Antioxidant capacities were measured using ethylenebenzothiozoline-6-sulfonic acid (ABTS) radical cation assay and ferric reducing antioxidant power assay (FRAP). Total phenolic content (TPC) was determined using Folin-Ciocalteu reagent while quantitative determination of total flavonoid content (TFC) was conducted using aluminium trichloride colorimetric method. Betacyanin content (BC) was measured by spectrophotometer. Red dragon fruit was extracted using conventional (CV) and ultrasonic-assisted extraction (UE) technique to determine the most efficient way of extracting its antioxidant components. Results indicated that UE increased TFC, reduced the extraction yield, BC, and TPC, but exhibited the strongest scavenging activity for the peel of red dragon fruit. In contrast, UE reduced BC, TFC, and scavenging activity but increased the yield for the flesh. Nonetheless, UE slightly increases TPC in flesh. Scavenging activity and reducing power were highly correlated with phenolic and flavonoid compounds. Conversely, the scavenging activity and reducing power were weakly correlated with betacyanin content. This work gives scientific evidences for the consideration of the type of extraction techniques for the peel and flesh of red dragon fruit in applied research and food industry.
Rare Earth Doped Silica Optical Fibre Sensors for Dosimetry in Medical and Technical Applications
Authors: Chiodini N. , Vedda A. , Veronese I.
Published: October 2014

Radioluminescence optical fibre sensors are gaining importance since these devices are promising in several applications like high energy physics, particle tracking, real-time monitoring of radiation beams, and radioactive waste. Silica optical fibres play an important role thanks to their high radiation hardness. Moreover, rare earths may be incorporated to optimise the scintillation properties (emission spectrum, decay time) according to the particular application. This makes doped silica optical fibres a very versatile tool for the detection of ionizing radiation in many contexts. Among the fields of application of optical fibre sensors, radiation therapy represents a driving force for the research and development of new devices. In this review the recent progresses in the development of rare earth doped silica fibres for dosimetry in the medical field are described. After a general description of advantages and challenges for the use of optical fibre based dosimeter during radiation therapy treatment and diagnostic irradiations, the features of the incorporation of rare earths in the silica matrix in order to prepare radioluminescent optical fibre sensors are presented and discussed. In the last part of this paper, recent results obtained by using cerium, europium, and ytterbium doped silica optical fibres in radiation therapy applications are reviewed.
Numerical Investigation: Effect of Stator Vanes on Turbocharger Turbine Performance
Authors: Yadagiri Rapolu Ganesh , Balachandar Siddharth Swaminathan , Kamaraj Keerthi Vallarasu
Published: October 2014

With reduced turbo lag and better transient response, the introduction of VTG stator guide vanes improved turbocharger performance at all the engine operating conditions. The VTG system accelerates and maneuvers exhaust gas flow to the turbine. Favorable flow conditions at turbine inlet created by vane shape improve turbine performance. At lower engine speed, it is observed that the pressure drop across vane system influences overall efficiency. Whereas at higher speed, the pressure drop and guide vane exit flow angle are found to determine the turbine efficiency. Successful practical operation of VTG system also depends on its ability to smoothly open and close the vanes at different gas loads. Stator vane shape greatly influences the smooth operability/controllability of vane system. In the present work, 3 symmetric vanes with differentT/Cratios and 2 asymmetric vanes are analyzed. The effect of geometric changes is studied from overall turbine performance as well as VTG system performance perspective. It is observed that symmetric vanes cause higher pressure drop at lower speeds leading to lower efficiency irrespective of the vane width. It is also observed that the pressure drop characteristics and vane exit flow angle are better with the asymmetric vanes, whereas the controllability of symmetric vanes is found to be superior. Analysis methodology is presented for achieving the best compromise between performance and controllability by the modification of vane geometric parameters through CFD simulations.
The Impact of a Submaximal Level of Exercise on Balance Performance in Older Persons
Authors: Alias Hani Asilah , Justine Maria
Published: October 2014

Objective. The purpose of this study was to determine the impact of a submaximal level of exercise on balance performance under a variety of conditions.Material and Method. Thirteen community-dwelling older persons with intact foot sensation (age = 66.69 ± 8.17 years, BMI = 24.65 ± 4.08 kg/m2, female,n=6) volunteered to participate. Subjects’ balance performances were measured using the Modified Clinical Test of Sensory Integration of Balance (mCTSIB) at baseline and after test, under four conditions of stance: (1) eyes-opened firm-surface (EOF), (2) eyes-closed firm-surface (ECF), (3) eyes-opened soft-surface (EOS), and (4) eyes-closed soft-surface (ECS). The 6-minute walk test (6MWT) protocol was used to induce the submaximal level of exercise. Data was analyzed using the Wilcoxon Signed-Rank Test.Results. Balance changes during EOF (z=0.00,P=1.00) and ECF (z=-1.342,P=0.180) were not significant. However, balance changes during EOS (z=-2.314,P=0.021) and ECS (z=-3.089,P=0.02) were significantly dropped after the 6MWT.Conclusion. A submaximal level of exercise may influence sensory integration that in turn affects balance performance, particularly on an unstable surface. Rehabilitation should focus on designing intervention that may improve sensory integration among older individuals with balance deterioration in order to encourage functional activities.
Alteration of Epigenetic Profile in Human Hepatocellular Carcinoma and Its Clinical Implications
Authors: Nishida Naoshi , Kudo Masatoshi
Published: October 2014

Hepatocellular carcinoma (HCC) is a common cancer worldwide and develops against a background of chronic liver damage. A variety of HCC-related genes are known to be altered by genetic and epigenetic mechanisms. Therefore, information regarding alteration of the genetic and epigenetic profiles in HCC is essential for understanding the biology of this type of tumor. Methylation at CpG sites in gene promoters is known to affect the transcription of the corresponding genes. Abnormal regional hypermethylation is observed in the 5′ region of several tumor suppressor genes (TSGs) in HCC, and this hypermethylation may promote carcinogenesis through the transcriptional inactivation of downstream TSGs. The DNA damage induced by oxidation is a trigger of abnormal DNA methylation and inactivation of TSGs through recruitment of the polycomb repressive complex to the promoter sequence. Thus, oxidative stress may be responsible for the emergence of HCC from chronic hepatitis and liver cirrhosis through the epigenetic alteration of TSGs. There have been several attempts to apply epigenetic information to the diagnosis and treatment of HCC. The predictive value of selected methylation events on survival in HCC patients has been reported, and the methylation profile of background liver could be associated with recurrence-free survival of HCC patients who have undergone hepatectomy. Another study detected methylated DNA from HCC cells in serum, and the circulating tumor DNA was regarded as a potential tumor marker. In addition, several trials of HCC therapy have targeted the epigenetic machinery and were based upon comprehensive analyses of DNA methylation of this type of tumor. Here, we present an overview of research regarding DNA methylation status in human HCC and describe the clinical application of epigenetic information to HCC.
Multimodality Management for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma
Authors: Choi Chihwan , Choi Gi Hong , Kim Tae Hyun , Tanaka Masatoshi , Meng Mao-Bin , Seong Jinsil
Published: October 2014

This review summarizes the contents of a workshop on multimodality management for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) held on July 6, 2013, under the auspices of the 4th Asia-Pacific Primary Liver Cancer Expert Meeting Scientific Advisory Committee. BCLC stage C HCC represents a varied disease spectrum and, therefore, further stratification of BCLC stage C should be explored. Although sorafenib is currently the standard treatment for BCLC stage C HCC, the survival benefits are modest and new treatment strategies are still needed. Based on the opinions of Asian experts, there are numerous alternative options aside from sorafenib for the treatment of BCLC stage C HCC, including surgical resection, hepatic arterial infusion chemotherapy, transarterial chemoembolization, and external radiotherapy. Moreover, there are several studies on the multimodality management of BCLC stage C HCC, mainly in the form of retrospective studies and a few phase I and II trials. Multimodality management with combinations of various locoregional therapies or locoregional therapies with systemic targeted therapy using sorafenib needs to be actively investigated. The Asia-Pacific clinical practice guidelines on multimodality management for BCLC stage C HCC need recommendations based on the level of evidence, the strength of the data, and the strength of recommendations of previously reported systems.
JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan
Authors: Kudo Masatoshi , Matsui Osamu , Izumi Namiki , Iijima Hiroko , Kadoya Masumi , Imai Yasuharu , Okusaka Takuji , Miyayama Shiro , Tsuchiya Kaoru , Ueshima Kazuomi , Hiraoka Atsushi , Ikeda Masafumi , Ogasawara Sadahisa , Yamashita Tatsuya , Minami Tetsuya , Yamakado Koichiro ,   on behalf of the Liver Cancer Study Group of Japan
Published: October 2014

The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term “lipiodol” from the definition of TACE failure/refractoriness.
Imaging of Acute Ischemic Stroke
Authors: El-Koussy Marwan , Schroth Gerhard , Brekenfeld Caspar , Arnold Marcel
Published: October 2014

Background: Over 80% of strokes result from ischemic damage to the brain due to an acute reduction in the blood supply. Around 25-35% of strokes present with large vessel occlusion, and the patients in this category often present with severe neurological deficits. Without early treatment, the prognosis is poor. Stroke imaging is critical for assessing the extent of tissue damage and for guiding treatment. Summary: This review focuses on the imaging techniques used in the diagnosis and treatment of acute ischemic stroke, with an emphasis on those involving the anterior circulation. Key Message: Effective and standardized imaging protocols are necessary for clinical decision making and for the proper design of prospective studies on acute stroke. Clinical Implications: Each minute without treatment spells the loss of an estimated 1.8 million neurons (‘time is brain'). Therefore, stroke imaging must be performed in a fast and efficient manner. First, intracranial hemorrhage and stroke mimics should be excluded by the use of computed tomography (CT) or magnetic resonance imaging (MRI). The next key step is to define the extent and location of the infarct core (values of >70 ml, >1/3 of the middle cerebral artery (MCA) territory or an ASPECTS score ≤7 indicate poor clinical outcome). Penumbral imaging is currently based on the mismatch concept. It should be noted that the penumbra is a dynamic zone and can be sustained in the presence of good collateral circulation. A thrombus length of >8 mm predicts poor recanalization after intravenous thrombolysis.
Differences in Alcohol-Related Research Publication Output between Countries: A Manifestation of Societal Concern?
Authors: Savic Michael , Room Robin
Published: October 2014

In a recent bibliometric analysis of alcohol- and other drug-related research publications in 11 countries, differences were found in research output across countries. In this paper we use additional secondary data to explore possible socio-historical factors that may contribute to differences in alcohol-related peer-reviewed publications across countries. Aside from general scientific productivity, we propose a possible link between the degree to which societies are concerned with alcohol and alcohol-related research outputs.
Decisional Early Interim 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography after Two Cycles of Chemotherapy in de novo Hodgkin Lymphoma
Authors: Iltis Aurore , Eder Veronique , Blasco Helene , Colombat Philippe , Sénécal Delphine
Published: October 2014

Background/Aims: An early evaluation with positron emission tomography (FDG-PET) has been demonstrated to be a valuable tool in the prediction of Hodgkin lymphoma's outcome. Herein we report a retrospective study on the outcome of Hodgkin lymphoma treated in accordance with interim FDG-PET results. Methods: 48 patients with de novo Hodgkin lymphoma were treated with 2 cycles of chemotherapy. According to the interim FDG-PET (PET2) evaluation, pre-established treatment was continued if PET2 was considered negative. Patients with a positive PET2 result underwent a salvage therapy. Progression-free survival (PFS) and overall survival (OS) were chosen as end points. Results: PET2 scan results were negative for 37 patients and positive for 11 patients. After salvage therapy, 7/11 patients were in complete remission and 4 patients had stable disease and were considered for third-line therapy. After a median follow-up of 5.2 years, 46 patients were still alive. The 4-year PFS were 84.5 and 45.4% for PET2-negative and PET2-positive patients, respectively (p = 0.007). In multivariate analysis, PET2 scan and extranodal disease remained relevant on PFS (p = 0.001 and 0.009, respectively). No difference was seen in OS. Conclusion: Our retrospective study suggests that salvage therapy for non-responder Hodgkin lymphoma using interim FDG-PET could improve the PFS of this group of patients.
Duration of Gestation and Mode of Delivery Affect the Genes of Transepithelial Sodium Transport in Pulmonary Adaptation
Authors: Janér Cecilia , Pitkänen Olli M. , Süvari Liina , Turpeinen Ursula , Palojärvi Anniina , Andersson Sture , Helve Otto
Published: October 2014

Background: Respiratory distress due to inadequate lung liquid clearance is a significant problem in infants delivered late preterm or early term, especially by elective cesarean delivery (CD). Lung liquid clearance depends on epithelial ion transport and in animals is induced by glucocorticoids. Objectives: In newborn late preterm and term infants to study airway epithelial gene expressions of epithelial sodium channel (ENaC), and the serum and glucocorticoid-inducible kinase 1 (SGK1), and their association with cortisol, mode of delivery, and gestational age (GA). Methods: Infants were delivered at 350/7-416/7 weeks. Cortisol in umbilical cord plasma was analyzed with liquid chromatography-tandem mass spectrometry. ENaC and SGK1 mRNAs in airway epithelial cells obtained within 3 h and at 1 day postnatally were quantified with real-time PCR. Results: ENaC and SGK1 mRNAs were significantly lower in late preterm and early term infants than in those ≥390/7 weeks. Significant correlations existed between both ENaC and SGK1 and cord cortisol and GA. In term infants, SGK1 mRNA at 1.5 h was higher after vaginal delivery than elective CD. Conclusions: In late preterm and early term infants, low expression of ENaC and SGK1 may parallel insufficient lung liquid clearance predisposing to respiratory distress. Lower SGK1 expression after term CD could translate into insufficient sodium and lung liquid absorption. The findings demonstrate a central role for cortisol in regulation of ENaC and potentially perinatal sodium and lung liquid clearance.
New Perspectives in the Assessment of Future Remnant Liver
Authors: Cieslak Kasia P. , Runge Jurgen H. , Heger Michal , Stoker Jaap , Bennink Roelof J. , van Gulik Thomas M.
Published: October 2014

In order to achieve microscopic radical resection margins and thus better survival, surgical treatment of hepatic tumors has become more aggressive in the last decades, resulting in an increased rate of complex and extended liver resections. Postoperative outcomes mainly depend on the size and quality of the future remnant liver (FRL). Liver resection, when performed in the absence of sufficient FRL, inevitably leads to postresection liver failure. The current gold standard in the preoperative assessment of the FRL is computed tomography volumetry. In addition to the volume of the liver remnant after resection, postoperative function of the liver remnant is directly related to the quality of liver parenchyma. The latter is mainly influenced by underlying diseases such as cirrhosis and steatosis, which are often inaccurately defined until microscopic examination after the resection. Postresection liver failure remains a point of major concern that calls for accurate methods of preoperative FRL assessment. A wide spectrum of tests has become available in the past years, attesting to the fact that the ideal methodology has yet to be defined. The aim of this review is to discuss the current modalities available and new perspectives in the assessment of FRL in patients scheduled for major liver resection. i 2014 S. Karger AG, Basel
No Relative Increase in Intra-Abdominal Adipose Tissue in Healthy Unstressed Preterm Infants at Term
Authors: Roggero Paola , Giannì Maria Lorella , Forzenigo Laura , Tondolo Tania , Taroni Francesca , Liotto Nadia , Piemontese Pasqua , Biondetti Pietro , Mosca Fabio
Published: October 2014

Background: Preterm infants may be at risk for altered adiposity, a known risk factor for unfavorable metabolic and cardiovascular outcomes. Objectives: The aim was to compare body composition (total body fat mass (FM), subcutaneous and intra-abdominal adipose tissue (AT)) between infants born preterm and at term. Methods: We conducted an observational, cross-sectional study that involved 50 infants born preterm free from major co-morbidities and 34 term healthy breastfed infants. Anthropometric measurements, body composition (total body FM, subcutaneous and intra-abdominal AT) were assessed at 40-42 weeks postconceptional age for preterm infants and within 15 days of birth for term infants. Total body FM was assessed by an air displacement plethysmography system and subcutaneous abdominal and intra-abdominal AT were assessed by magnetic resonance imaging using a commercially available software program. Results: Compared to term infants, mean (SD) total body FM (g) (636.7 (247) vs. 418.4 (253), p < 0.0001) and mean (SD) subcutaneous abdominal AT (g) (123 (36) vs. 98.9 (22), p < 0.001) were significantly higher in preterm infants but mean (SD) fat-free mass (g) (2,530 (420) vs. 2,965 (389), p < 0.0001) and mean (SD) intra-abdominal AT (10.9 (5.2) vs. 18.2 (13.2), p = 0.001) were significantly lower. Conclusions: In the absence of severe illness during the hospital stay, prematurity, although associated with increased total body FM, does not appear to be associated with a relative increase in intra-abdominal AT compared to term infants.
The Effects of Vital Dyes on Retinal Pigment Epithelium Cells in Oxidative Stress
Authors: Golan Shani , Levi Ran , Entin-Meer Michal , Barak Adiel
Published: October 2014

Purpose: To determine the effect of the most commonly used vital dyes in vitrectomy [trypan blue at 0.15% concentration and indocyanine green (ICG) at 0.5% concentration] on the viability of human retinal pigment epithelium (RPE) cell lines (ARPE-19) exposed to oxidative stress. Methods: ARPE-19 cells unexposed or exposed to oxidative stress (hypoxic chamber) were treated for 1 min with one of the dyes. RPE proliferation was measured by 3H-thymidine incorporation, adhesion by ability to adhere to fibronectin, and safety by annexin V staining. Results: Proliferation: The dyes affected the proliferation of RPE cells differently under non-hypoxic and hypoxic conditions (p = 0.001). In non-hypoxic conditions, there was no statistically significant difference between the proliferation of the treated (both dyes) and untreated RPE cells (p = 0.279). Under hypoxia, both dyes significantly suppressed proliferation, more so with ICG (p = 0.001). Adhesion: The dyes affected adhesion differently under non-hypoxic and hypoxic conditions (p = 0.04). In non-hypoxic conditions, both increased the adhesive properties of RPE cells to fibronectin, ICG more than trypan blue (p = 0.001). Under hypoxia, both dyes suppressed adhesion, with no statistically significant difference between treated and non-treated RPE cells. Apoptosis: Both dyes increased early apoptosis of RPE cells compared with no treatment (p = 0.001), ICG more than trypan blue. Hypoxia increased the apoptosis of both dyes compared to non-hypoxic conditions (p = 0.02). Conclusions: In hypoxic conditions, both dyes showed an inhibition of RPE adhesion to fibronectin and proliferation capacity and an increase in early apoptosis compared with non-hypoxic conditions. Apoptosis was greater in ICG-treated RPE cells than in trypan blue-treated cells.
Local Muscle Injection of Botulinum Toxin Type A Synergistically Improves the Beneficial Effects of Repetitive Transcranial Magnetic Stimulation and Intensive Occupational Therapy in Post-Stroke Patients with Spastic Upper Limb Hemiparesis
Authors: Yamada Naoki , Kakuda Wataru , Kondo Takahiro , Mitani Sugao , Shimizu Masato , Abo Masahiro
Published: October 2014

Background: The purpose of this study was to determine whether local injection of botulinum toxin type A (BoNT-A) into the spastic muscles has any added benefits to repetitive transcranial magnetic stimulation (RTMS)/occupational therapy (OT) in patients with spastic upper limb hemiparesis. Methods: The study subjects of 80 post-stroke patients with spastic upper limb hemiparesis (age: 60.2 ± 13.0 years, time after stroke: 55.3 ± 43.0 months), were divided into the BoNT-A plus RTMS/OT group and RTMS/OT group. BoNT-A was injected into the spastic muscles (total dose: 240 units) before RTMS/OT. The latter included 12 sessions of 40 min RTMS over the non-lesional hemisphere and 240-min intensive OT daily over 15 days. Spasticity was evaluated by the modified Ashworth scale (MAS) and the motor function of the affected upper limb was evaluated serially with Fugl-Meyer Assessment and Wolf Motor Function Tests. Results: Both groups showed significant improvements in spasticity and motor function. The addition of BoNT-A resulted in better improvement in FMA score and MAS of finger flexor muscles (p < 0.05). Conclusions: The triple-element protocol of local injection of BoNT-A into spastic finger muscles, RTMS and intensive OT, is a promising therapeutic program for post-stroke spastic upper limb hemiparesis, although its significance should be confirmed in randomized, placebo-controlled trials.
Asymptomatic Carotid Artery Stenosis Treated with Medical Therapy Alone: Temporal Trends and Implications for Risk Assessment and the Design of Future Studies
Authors: Hadar Nira , Raman Gowri , Moorthy Denish , O'Donnell Thomas F. , Thaler David E. , Feldmann Edward , Lau Joseph , Kitsios Georgios D. , Dahabreh Issa J.
Published: October 2014

Background: The rate of adverse clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone can be used to guide clinical decision-making and to inform future research. We aimed to investigate temporal changes in the incidence rate of clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone and to explore the implications of these changes for the design of future comparative studies. Summary: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, US Food and Drug Administration documents, and reference lists of included studies (last search: December 31, 2012). We selected prospective cohort studies of medical therapy for asymptomatic carotid artery stenosis and we extracted information on study characteristics, risk of bias, and outcomes. We performed meta-analyses to estimate summary incidence rates, meta-regressions to assess trends over time, and simulations to explore sample size requirements for the design of future studies comparing new treatments against medical therapy. The main outcomes of interest were ipsilateral stroke, any stroke, cardiovascular death, death, and myocardial infarction. We identified 41 studies of medical therapy for patients with asymptomatic carotid stenosis (last recruitment year: 1978-2009). The summary incidence rate of ipsilateral carotid territory stroke (25 studies) was 1.7 per 100 person-years. This incidence rate was significantly lower in recent studies (last recruitment year from 2000 onwards) as compared to studies that ended recruitment earlier (1.0 vs. 2.3 events per 100 person-years; p < 0.001). The incidence rates of any territory stroke (17 studies), cardiovascular death (6 studies), death (13 studies), and myocardial infarction (5 studies) were 2.7, 4.1, 4.6, and 1.8 per 100 person-years, respectively. Simulations showed that future studies would need to enroll large numbers of patients with a relatively high incidence rate under medical therapy, and evaluate interventions with large effect sizes, to have adequate power to reliably detect treatment effects. Key Messages: Improved prognosis under medical therapy alone has narrowed the potential range of risk reduction attainable with new treatments for asymptomatic carotid stenosis. Future comparative studies will need to enroll large numbers of patients to assess treatment effectiveness.
Movement Disorders in Spinocerebellar Ataxias in a Cohort of Brazilian Patients
Authors: Moro Adriana , Munhoz Renato P. , Moscovich Mariana , Arruda Walter O. , Raskin Salmo , Teive Hélio A.G.
Published: October 2014

Background: Movement disorders (MDs) are well recognized in all subtypes of spinocerebellar ataxias (SCA), but phenomenology and frequency vary widely. Methods: Three hundred seventy-eight patients, from 169 Brazilian families, with SCAs were assessed with neurological examination and molecular genetic testing. Results: Dystonia was the most common movement disorder, found in 5.5% of all patients, particularly in SCA3. We observed Parkinsonian features in 6.6% of SCA3 patients, and myoclonus in two patients of our cohort. Conclusions: Our study demonstrated that MDs are major extracerebellar manifestations of SCA. The observed phenotypes in addition to ataxia may provide significant clues for a particular SCA genotype.
The Safety of Concentrated Trastuzumab in 100 ml of Saline Solution for Administration to Patients with HER2-Positive Breast Cancer: A Phase 1 Study
Authors: Sengoku Norihiko , Tanino Hirokazu , Kosaka Yoshimasa , Kikuchi Mariko , Nishimiya Hiroshi , Waraya Mina , Katoh Hiroshi , Enomoto Takumo , Sato Takeo , Kuranami Masaru , Watanabe Masahiko
Published: October 2014

Background: It is recommended that administration of trastuzumab should be carried out in a volume of 250 ml of saline solution over 90 min. Since 2011, recommendations have allowed a shortening of the administration time to 30 min at the second administration. However, the volume to be administered is still 250 ml. The purpose of this study was to evaluate the safety of trastuzumab administered in 100 ml of saline solution over 30 min. Methods: This study enrolled patients with HER2-positive breast cancer. Three dose levels of trastuzumab, each in 100 ml of saline solution, were used (2, 6 and 8 mg/kg). The primary end point was the determination of safety. Results: Nine patients were enrolled. Since no adverse events were observed, the 8 mg/kg/100 ml saline solution dose level was the recommended dose. Conclusions: A 30-min administration of trastuzumab in 100 ml of saline solution is safe in patients with HER2-positive breast cancer.
Gallbladder Dysfunction: How Much Longer Will It Be Controversial?
Authors: Goussous Naeem , Kowdley Gopal C. , Sardana Neeraj , Spiegler Ethan , Cunningham Steven C.
Published: October 2014

Background: Motility disorders of the biliary tree [biliary dyskinesia, including both gallbladder dysfunction (GBD), and sphincter of Oddi dysfunction] are difficult to diagnose and to treat. Summary: There is controversy in the literature in particular regarding the criteria that should be used to select patients for cholecystectomy (CCY) in cases of suspected GBD. The current review covers the history, diagnosis, and treatment of GBD. Key Messages: Only >85% of patients with suspected GBD have relief following CCY, a much lower rate than the nearly 100% success rate following CCY for gallstone disease. Unfortunately, the literature is lacking, and there are no universally agreed-upon criteria for selecting which patients to refer for operation, although cholecystokinin (CCK)-enhanced hepatobiliary iminodiacetic acid scan is often used, with emphasis on an abnormally low gallbladder ejection fraction or pain reproduction at CCK administration. There is a clear need for large, well-designed, more definitive, prospective studies to better identify the indications for and efficacy of CCY in cases of GBD. i 2014 S. Karger AG, Basel
Neurocysticercosis is a Neglected Microbleed Mimic. A Cautionary Note for Stroke Neurologists
Authors: Del Brutto Oscar H. , Lama Julio , Zambrano Mauricio , Del Brutto Victor J.
Published: October 2014

Background: Calcified cysticerci share the morphology and signal properties with true cerebral microbleeds, but this condition is neglected at the time of evaluating MRIs for clinical or research purposes. We report our experience with the MRI reading obtained from the Atahualpa Project, a population-based stroke study, conducted in a village endemic for cysticercosis. Methods: Neuroimaging studies were performed in Atahualpa residents aged =60 years identified during a door-to-door survey. Lesions of interest included neuroimaging markers of small vessel disease. Out of 311 residents, 248 (80%) agreed to participate. Two internal readers independently reviewed MRIs blinded to CT findings. Results: Internal readers achieved good-to-very-good inter-rater agreements for all types of investigated lesions, with the exception of cortical microbleeds (κ = 0.53). After reviewing CTs, six of eight conflicting lesions were cysticercus. Five external experts blinded to CT findings also read those images, reporting conflicting results. Cysticercosis was recognized only in 26% of readings. Conclusion: Calcified cysticercotic lesions should be included in the list of microbleed mimics. CT should be performed in doubtful cases to avoid overdiagnosis of cerebral microbleeds in large-scale stroke studies and in the clinical practice. Proper recognition of this neglected microbleed mimic may have important therapeutic implications.
Evaluation of Esophagogastric Varices after Adult-to-Adult Living Donor Liver Transplantation Using a Left Lobe Graft
Authors: Ishizaki Yoichi , Konishi Nanami , Yoshimoto Jiro , Sugo Hiroyuki , Imamura Hiroshi , Kawasaki Seiji
Published: October 2014

Background: There is little information on whether living donor liver transplantation (LDLT) reduces the supply of blood to esophagogastric varices. The aim of the present study was to assess the effects of LDLT on esophagogastric varices using both endoscopy and transendoscopic microvascular Doppler sonography (EMDS). Patients and Methods: 16 LDLT recipients were enrolled in the present study. Esophagogastric varices were assessed by endoscopy before and after LDLT. Direct measurement of variceal blood velocity was performed using EMDS in 12 of the 16 patients, and portal vein pressure before and after graft implantation was measured in 10 of them. Results: The median interval between LDLT and endoscopic examination was 129 days (range 20-624). Endoscopy demonstrated improvement of esophageal varices in 15 patients and of gastric varices in 4 of 5 patients assessed. The mean blood flow velocity in esophageal varices after LDLT was significantly lower than that before LDLT (8.8 w 3.6 vs. 0.9 w 1.2 cm/s, p < 0.001). The mean portal vein pressure did not decrease significantly after LDLT in comparison with that before LDLT (from 25.2 w 5.2 to 23.1 w 3.6 mm Hg, p = 0.22). Conclusion: Although portal vein pressure does not decrease immediately after left lobe LDLT, esophagogastric varices are ameliorated after a few months, and variceal blood flow velocity is reduced in almost all patients. i 2014 S. Karger AG, Basel
Rational Therapy of Clostridium difficile Infections
Authors: Keller Peter M. , Weber Marko H.
Published: October 2014

Background:Clostridium difficile infections (CDI) are increasingly important in patients with antibiotic treatments, ranging from mild, self-limiting to severe, life-threatening disease. Currently, diagnostic algorithms and treatment guidelines are being adapted to novel tests and therapeutic options for recurrent CDI. Methods: A systematic literature search using the terms ‘Clostridium difficile' and ‘treatment' was carried out. Current guidelines are being discussed from a clinical point of view. Results: State-of-the-art diagnostics for C. difficile diagnosis rely on the patient's history, clinical symptoms, and laboratory examination of stool. Recommendations are in favour of glutamate dehydrogenase (GDH) screening tests and confirmatory detection of C. difficile toxin genes (polymerase chain reaction (PCR)). Therapeutic strategies depend on disease severity (mild vs. severe) and endorse metronidazole and vancomycin as well as fidaxomycin for recurrent disease. In very severe cases, surgical therapy is recommended. For relapsing diseases, faecal transfer is considered as a therapeutic option if available. Conclusion: Current guidelines have been adapted to new pathways in diagnosing CDI and have included statements on novel therapeutic options such as fidaxomycin and faecal transplant for recurrent disease. Depending on the severity of the disease, standard therapy with either metronidazole or vancomycin is recommended.
Infections and Chronic Inflammatory Bowel Disease
Authors: Kucharzik Torsten , Maaser Christian
Published: October 2014

In the more recent years since the introduction of anti-TNF therapy, the treatment strategy in chronic inflammatory bowel disease has developed more towards an early intensive, often double immunosuppression. While this leads to an improved therapeutic success, this intensified therapy also increases the risk for side effects and especially for infectious complications. The early detection of this complication in the immunocompromised patient is often more difficult due to the potential broad spectrum of infectious agents, the often atypical presentation in conjunction with the immunosuppression as well as often similar symptoms regarding intestinal infectious complications common for a flare of the underlying disease. In the first part, this overview will discuss the broad spectrum of potential infectious complications, using pulmonary infections as an example and presenting an algorithm for detection and therapy. In the second part, common intestinal infectious complications will be discussed from diagnosis to therapy.
Kidney Disease and Cognitive Function: African American-Diabetes Heart Study MIND
Authors: Palmer Nicholette D. , Sink Kaycee M. , Smith Susan Carrie , Xu Jianzhao , Bowden Donald W. , Hugenschmidt Christina E. , Whitlow Christopher T. , Williamson Jeff D. , Maldjian Joseph A. , Divers Jasmin , Freedman Barry I.
Published: October 2014

Aims: Albuminuria and reduced estimated glomerular filtration rate (eGFR) are linked with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were performed in unrelated AAs with T2D to determine relationships. Methods: Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol. Results: Participants had a mean ± SD age of 60.2 ± 9.7 years, 62.7% were female, T2D duration was 14.3 ± 8.9 years, eGFR 86.0 ± 23.2 ml/min/1.73 m2, and UACR 155.8 ± 542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p = 0.014), MoCA (p = 0.0089), DSC (p = 0.0004), Stroop performance time (p = 0.003), Stroop errors (p = 0.032), and Stroop interference (p = 0.026). Higher eGFR was associated with better performance on DSC (p = 0.0071). Conclusions: In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.
Adjuvant Therapy of Uveal Melanoma: Current Status
Authors: Triozzi Pierre L. , Singh Arun D.
Published: October 2014

The survival of patients with uveal melanoma remains poor because of the development of metastatic disease. Adjuvant therapy after treatment of the primary tumor has been tested but has not been shown to prevent the development of metastasis. Several new approaches are being developed. Cytotoxic and immunotherapeutic regimens are being more rationally applied using tumor genetic criteria to better identify patients at risk. Trials in the adjuvant setting of novel immunotherapeutic and targeted agents active in the metastatic setting are being developed, as are approaches to promote cellular differentiation and dormancy. The rarity and biology of uveal melanoma present challenges. Participation in well-designed, scientifically sound clinical trials is critical.
T Helper 17 Cells and Related Cytokines after Allergen Inhalation Challenge in Allergic Asthmatics
Authors: Naji Nizar , Smith Steven G. , Gauvreau Gail M. , O'Byrne Paul M.
Published: October 2014

Background: T helper (Th)17 cells may play a role in allergic asthma. This study assessed the effect of allergen inhalation challenge on circulating Th17 cells and related cytokines in allergic asthmatics. Methods: Peripheral blood mononuclear cells were collected from 16 atopic asthmatics before and 24 h after allergen challenge, as well as from 10 atopic nonasthmatics and 10 normal controls. Cells were stained for Th17 cytokines and their receptors (IL-17A, IL-17F, IL-21, IL-22, IL-17R, and IL-23R) using flow cytometry. Cytokine concentrations from cell culture supernatants were quantified using a multiplex assay for IL-17A, IL-17F, IL-21, IL-22, and IL-23. Results: At baseline, asthmatics had a higher percentage of circulating Th17 cells (1.2 ± 0.5%) compared to normal controls (0.9 ± 0.66%, p < 0.001) but not compared to atopic nonasthmatics (1.13 ± 0.5%). There was a significant increase in Th17 cells in asthmatics after allergen challenge to 1.55 ± 0.4% (p < 0.05) and a trend toward significance in IL-17R expression from 3.4 ± 4.3 to 6.86 ± 6.84% after allergen challenge (p = 0.06). There was also a significant reduction in IL-21-positive cells following allergen challenge from 3.46 ± 1.85 to 2.33 ± 1.37% (p < 0.001). There were no significant differences in IL-17F, IL-22 and IL-23R expression. The concentration of IL-17A in culture supernatant was significantly higher in asthmatics compared to normal controls and IL-17A significantly increased 24 h after allergen challenge. Conclusions: The increase of Th17 cells and IL-17A in atopic asthma after allergen inhalation challenge suggests a possible role for Th17 in allergen-induced airway responses.
Staphylococcal Exotoxins Induce Interleukin 22 in Human Th22 Cells
Authors: Niebuhr Margarete , Mainardy Julia , Heratizadeh Annice , Satzger Imke , Werfel Thomas
Published: October 2014

Background: We have shown previously that T cells from atopic dermatitis (AD) patients produce more IL-22 upon staphylococcal exotoxin stimulation compared to psoriasis patients and healthy controls. The role of staphylococcal exotoxins on polarized memory T helper (Th)22 cells which are enriched in inflamed AD skin remains elusive. Our aim was to investigate IL-22 production in response to staphylococcal enterotoxin B (SEB) and α-toxin stimulation in human memory T cells and polarized Th22 cells. Methods: IL-22 induction was investigated in human peripheral blood-derived CD4+CD45RO+CD45RA- T cells and polarized Th22 cells after SEB and sublytic α-toxin stimulation in a time-dependent manner at the mRNA and protein (ELISA) levels. Results: Th22 cells secreted more IL-22 compared to freshly isolated peripheral blood-derived memory T cells. SEB and α-toxin induced IL-22 in memory T cells as well as in Th22 cells. More IL-22 was induced by SEB and α-toxin in freshly isolated peripheral blood memory T cells compared to Th22 cells derived from memory T cells in long-term cell culture without polarization and Th22 cells under Th22-promoting conditions with IL-6 and TNF-α. No differences in IL-22 induction by staphylococcal exotoxins were observed between cells from AD compared to psoriasis patients and healthy controls. Conclusions: Increased IL-22 secretion can promptly be induced by staphylococcal exotoxins in skin infiltrating CD4+CD45RO+CD45RA- memory T cells and can potentially amplify chronic skin inflammation in AD in the context of bacterial colonization and infection. This should be investigated further in detail in lesional skin of AD and psoriasis patients.
Evidence-Based Medicine in Daily Surgical Decision Making: A Survey-Based Comparison between the UK and Germany
Authors: Schnitzbauer Andreas A. , Proneth Andrea , Pengel Liset , Ansorg Jörg , Anthuber Matthias , Bechstein Wolf O. , Schlitt Hans J. , Geissler Edward K.
Published: October 2014

Background: Evidence-based medicine (EbM) is a vital part of reasonable and conclusive decision making for clinicians in daily clinical work. To analyze the knowledge and the attitude of surgeons towards EbM, a survey was performed in the UK and Germany. Methods: A web-based questionnaire was distributed via mailing lists from the Royal College of Surgeons of England (RCSE) and the Berufsverband Deutscher Chirurgen (BDC). Our primary aim was to get information about knowledge of EbM amongst German and British surgeons. Results: A total of 549 individuals opened the questionnaire, but only 198 questionnaires were complete and valid for analysis. In total, 40,000 recipients were approached via the mailing lists of the BDC and RCSE. The response rate was equally low in both countries. On a scale from 1 (unimportant) to 10 (very important), all participants rated EbM as very important for daily clinical decision making (7.3 ± 1.9) as well as for patients (7.8 ± 1.9) and the national health system (7.8 ± 1.9). On a scale from 1 (unimportant) to 5 (very important), systematic reviews (4.6 ± 0.6) and randomized controlled trials (4.6 ± 0.6) were identified as the highest levels of study designs to enhance evidence in medicine. British surgeons considered EbM to be more important in daily clinical work when compared to data from German surgeons (7.9 ± 1.6 vs. 6.7 ± 2.1, p < 0.001). Subgroup analysis showed different results in some categories; however, a pattern to explain the differences was not evident. Personal requirements expressed in a free text field emphasized the results and reflected concerns such as broad unwillingness and lack of interdisciplinary approaches for patients (n = 59: 25 in the UK and 34 in Germany). Conclusion: The overall results show that EbM is believed to be important by surgeons in the UK and Germany. However, perception of EbM in the respective health system (UK vs. Germany) may be different. Nonetheless, EbM is an important tool to navigate through daily clinical problems although a discrepancy between the knowledge of theoretical abstract terms and difficulties in implementing EbM in daily clinical work has been detected. The provision of infrastructure, courses and structured education as a permanent instrument will advance the knowledge, application and improvement of EbM in the future.
Antibiosis of Necrotizing Pancreatitis
Authors: Arlt Alexander , Erhart Wiebke , Schafmayer Clemens , Held Hanns-Christoph , Hampe Jochen
Published: October 2014

Background: Necrotizing pancreatitis is a life-threatening presentation of acute pancreatitis. The mortality of 20-80% initially depends on the persistence of organ failure and systemic inflammatory response syndrome (SIRS) and, in the later course of the disease, on secondary infection of the necrosis. The questions whether prophylactic antibiotics aiming to prevent this infection should be administered and which antibiotic is the best to use, as well as the problem of fungal infection under antibiotic treatment are still intriguing and insufficiently solved. Methods: A search of the literature using PubMed was carried out, supplemented by a review of the programmes of the Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW). Results: Despite the widely practised prophylactic antibiotic administration in severe pancreatitis, no evidence for the benefit of this strategy exists. One of the drawbacks might be a tendency for disastrous fungal infection under prophylactic antibiotics. Bacterial translocation from the gut in the second week after the onset of symptoms is the major source for infection of pancreatic necrosis and provides a clear indication for antibiotic treatment. However, routine fine-needle aspiration for a calculated antibiotic therapy cannot be recommended, and all other tests offer only indirect signs. Important factors such as enteral versus parenteral feeding and the method of necrosectomy are mostly neglected in the trials but seem to be essential for the outcome of the patient. Conclusions: Even though most meta-analyses including the newer double-blind, placebo-controlled trials on prophylactic antibiotics showed no beneficial effects in the prevention of infection of necrosis and/or outcome of the patients, this strategy is still widely used in clinical routine. Since nearly all trials published so far show systematic problems (i.e. inaccurate definition of the severity of the disease, poor statistical testing, and neglect of differences in the route of nutrition), there is a need for randomized controlled prospective trials with exact definitions of the disease.