bluuebunny/crossref_metadata_2025 huggingface dataset:
GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility
Authors: Guan Xinfu , Shi Xuemei , Li Xiaojie , Chang Benny , Wang Yi , Li Depei , Chan Lawrence
Published: July 2012

Glucagon-like peptides (GLP-1/2) are cosecreted from endocrine L cells in the gut and preproglucagonergic neurons in the brain. Peripheral GLP-2 action is essential for maintaining intestinal homeostasis, improving absorption efficiency and blood flow, promoting immune defense, and producing efficacy in treatment of gastrointestinal diseases. However, it is unknown if CNS GLP-2 plays a physiological role in the control of energy homeostasis. Since GLP-1/2 are cotranslated from preproglucagongene and coproduced by prohormone convertase-1, it is challenging to knockout GLP-2 only. Instead, our laboratory has generated a Glp2r-floxed mouse line to dissect cell-specific GLP-2 receptor GLP-2R) action in the regulation of energy balance. Our objective was to determine if GLP-2R in the hypothalamus modulates feeding behavior and gastric emptying. We show that Glp2r mRNA and protein are highly expressed in the arcuate nucleus and dorsomedial nucleus of the mouse hypothalamus. Using the Cre-LoxP system, we generated mice that lack Glp2r expression in POMC neurons (KO; mainly in the hypothalamus). The KO mice showed hyperphagic behavior (such as increases in food intake and meal frequency), accelerated gastric emptying (assessed by [13C]octanoic acid breath test), and late-onset obesity, yet there was no decrease in basal metabolic rate. Infusion of GLP-2 (2.5 nmol into the 4th ventricle) suppressed food intake and gastric emptying, while GLP-2-mediated effects were abolished in the melanocortin receptor-4 (MC4R) KO mice. We conclude that Glp2r deletion in POMC neurons enhances feeding behavior and gastric motility, whereas icv GLP-2R activation suppresses food intake and gastric emptying through the MC4R signaling pathway. This study indicates that CNS GLP-2R plays a physiological role in the control of feeding behavior and gastric emptying and that this is mediated probably through the melanocortin system.
Overexpression of manganese superoxide dismutase ameliorates high-fat diet-induced insulin resistance in rat skeletal muscle
Authors: Boden Michael J. , Brandon Amanda E. , Tid-Ang Jennifer D. , Preston Elaine , Wilks Donna , Stuart Ella , Cleasby Mark E. , Turner Nigel , Cooney Gregory J. , Kraegen Edward W.
Published: July 2012

Elevated mitochondrial reactive oxygen species have been suggested to play a causative role in some forms of muscle insulin resistance. However, the extent of their involvement in the development of diet-induced insulin resistance remains unclear. To investigate, manganese superoxide dismutase (MnSOD), a key mitochondrial-specific enzyme with antioxidant modality, was overexpressed, and the effect on in vivo muscle insulin resistance induced by a high-fat (HF) diet in rats was evaluated. Male Wistar rats were maintained on chow or HF diet. After 3 wk, in vivo electroporation (IVE) of MnSOD expression and empty vectors was undertaken in right and left tibialis cranialis (TC) muscles, respectively. After one more week, insulin action was evaluated using hyperinsulinemic euglycemic clamp, and tissues were subsequently analyzed for antioxidant enzyme capacity and markers of oxidative stress. MnSOD mRNA was overexpressed 4.5-fold, and protein levels were increased by 70%, with protein detected primarily in the mitochondrial fraction of muscle fibers. This was associated with elevated MnSOD and glutathione peroxidase activity, indicating that the overexpressed MnSOD was functionally active. The HF diet significantly reduced whole body and TC muscle insulin action, whereas overexpression of MnSOD in HF diet animals ameliorated this reduction in TC muscle glucose uptake by 50% ( P < 0.05). Decreased protein carbonylation was seen in MnSOD overexpressing TC muscle in HF-treated animals (20% vs. contralateral control leg, P < 0.05), suggesting that this effect was mediated through an altered redox state. Thus interventions causing elevation of mitochondrial antioxidant activity may offer protection against diet-induced insulin resistance in skeletal muscle.
A Comprehensive Subcellular Proteomic Survey of Salmonella Grown under Phagosome-Mimicking versus Standard Laboratory Conditions
Authors: Brown Roslyn N. , Sanford James A. , Park Jea H. , Deatherage Brooke L. , Champion Boyd L. , Smith Richard D. , Heffron Fred , Adkins Joshua N.
Published: July 2012

Towards developing a systems-level pathobiological understanding of Salmonella enterica, we performed a subcellular proteomic analysis of this pathogen grown under standard laboratory and phagosome-mimicking conditions in vitro. Analysis of proteins from cytoplasmic, inner membrane, periplasmic, and outer membrane fractions yielded coverage of 25% of the theoretical proteome. Confident subcellular location could be assigned to over 1000 proteins, with good agreement between experimentally observed location and predicted/known protein properties. Comparison of protein location under the different environmental conditions provided insight into dynamic protein localization and possible moonlighting (multiple function) activities. Notable examples of dynamic localization were the response regulators of two-component regulatory systems (e.g., ArcB and PhoQ). The DNA-binding protein Dps that is generally regarded as cytoplasmic was significantly enriched in the outer membrane for all growth conditions examined, suggestive of moonlighting activities. These observations imply the existence of unknown transport mechanisms and novel functions for a subset of Salmonella proteins. Overall, this work provides a catalog of experimentally verified subcellular protein locations for Salmonella and a framework for further investigations using computational modeling.
The Effect of Hip Bracing on Gait in Patients with Medial Knee Osteoarthritis
Authors: Wallace David , Barr Christa
Published: July 2012

Objective.Impaired hip motion has been associated with heightened medial knee joint loading in patients with knee osteoarthritis (OA). A hip external rotation strap designed to pull the femur into external rotation and abduction may serve as one protective mechanism. The primary aim of our study is to determine if the strap decreases medial knee joint loading during level walking in people with knee OA.Design.This study is a single-day repeated measures design.Methods.15 volunteers with medial knee OA underwent motion analysis data collection during two randomly assigned walking conditions: (1) wearing the strap and (2) control (no strap). Primary outcome measures were peak pelvis, hip and knee joint motions, and torques. These outcomes were averaged across five trials for each condition.Results.Hip abduction (), trunk lean towards the stance limb () and pelvic tilt () significantly increased with the strap versus control trials. Knee adduction loading did not significantly change with the strap ().Conclusion.The use of the hip external rotation strap resulted in angular changes at the hip and pelvis which may be beneficial for patients with medial knee osteoarthritis.
Comparison of Time Domain and Spectral Domain Optical Coherence Tomography in Measurement of Macular Thickness in Macular Edema Secondary to Diabetic Retinopathy and Retinal Vein Occlusion
Authors: Hatef Elham , Khwaja Afsheen , Rentiya Zubir , Ibrahim Mohamed , Shulman Matthew , Turkcuoglu Peykan , Sepah Yasir , Wang Jianmin , Channa Roomasa , Bittencourt Millena , Akhtar Abeer , Heo Jangwon , Do Diana V. , Nguyen Quan Dong
Published: July 2012

Purpose. To evaluate macular thickness, agreement, and intraclass repeatability in three optical coherence tomography (OCT) devices: the time domain (TD) Stratus OCT and two spectral domain (SD) OCTs, Spectralis and Cirrus SD-OCT, in eyes with macular edema secondary to diabetic retinopathy (DR) and retinal vein occlusion (VO).Methods. In a prospective observational study at a university-based retina practice, retinal thickness tomography was performed simultaneously for fifty-eight patients (91 eyes) with DR and VO employing a time domain and two spectral domain OCTs. Agreement in macular measurements was assessed by constructing Bland-Altman plots. Intraclass repeatability was assessed by intraclass correlation coefficients (ICCs).Results. Based on the Bland-Altman plots for central macular thickness, there was low agreement between the measurements of Cirrus SD-OCT and Stratus OCT, Spectralis OCT and Stratus OCT, as well as Spectralis OCT and Cirrus SD-OCT among DR and RVO patients. All three devices demonstrated high intraclass repeatability, with ICC of 98% for Stratus OCT, 97% for Cirrus SD-OCT, and 100% for Spectralis OCT among DR patients. The ICC was 97% for Stratus OCT, 79% for Cirrus SD-OCT, and 91% for Spectralis OCT among RVO patients.Conclusion. There are low agreements among interdevice measurements. However, intraclass repeatability is high in both TD and SD-OCT devices.
Stability of Difference Schemes for Fractional Parabolic PDE with the Dirichlet‐Neumann Conditions
Authors: Cakir Zafer
Published: July 2012

The stable difference schemes for the fractional parabolic equation with Dirichlet and Neumann
boundary conditions are presented. Stability estimates and almost coercive stability estimates with ln (1/(τ + |h|)) for the solution of these difference schemes are obtained. A procedure of modified Gauss elimination method is used for solving these difference schemes of one‐dimensional fractional parabolic partial differential equations.
Retinal Damage in Multiple Sclerosis Disease Subtypes Measured by High-Resolution Optical Coherence Tomography
Authors: Oberwahrenbrock Timm , Schippling Sven , Ringelstein Marius , Kaufhold Falko , Zimmermann Hanna , Keser Nazmiye , Young Kim Lea , Harmel Jens , Hartung Hans-Peter , Martin Roland , Paul Friedemann , Aktas Orhan , Brandt Alexander U.
Published: July 2012

Background.Optical coherence tomography (OCT) has facilitated characterisation of retinal alterations in MS patients. Only scarce and in part conflicting data exists on different MS subtypes.Objective.To analyse patterns of retinal changes in different subtypes of MS with latest spectral-domain technology.Methods.In a three-centre cross-sectional study 414 MS patients and 94 healthy controls underwent spectral-domain OCT examination.Results.Eyes of MS patients without a previous optic neuritis showed a significant reduction of both retinal nerve fibre layer (RNFL) thickness and total macular volume (TMV) compared to healthy controls independent of the MS subtype (P<0.001for all subtypes). RNFL thickness was lower in secondary progressive MS (SPMS) eyes compared to relapsing-remitting MS (RRMS) eyes (P=0.007), and TMV was reduced in SPMS and primary progressive MS (PPMS) eyes compared to RRMS eyes (SPMS:P=0.039, PPMS:P=0.005). Independent of the subtype a more pronounced RNFL thinning and TMV reduction were found in eyes with a previous optic neuritis compared to unaffected eyes.Conclusion.Analysis of this large-scale cross-sectional dataset of MS patients studied with spectral-domain OCT confirmed and allows to generalize previous findings. Furthermore it carves out distinct patterns in different MS subtypes.
Modulation of Lipoprotein Cholesterol Levels in Plasmodium berghei Malarial Infection by Crude Aqueous Extract of Ganoderma lucidum
Authors: Oluba Olarewaju M. , Olusola Augustine O. , Eidangbe George O. , Babatola Leye J. , Onyeneke E. Chukwu
Published: July 2012

In this study, attempt is made to establish changes in serum and liver lipoprotein cholesterols accompanying Plasmodium berghei malarial infection in mice treated with aqueous extract of Ganoderma lucidum at 100, 250, and 500 mg/kg body weight in comparison with 15 mg/kg chloroquine (CQ). Significant increases in all the lipoprotein fractions were observed in infected untreated mice compared with normal control mice. Treatment with 100 and 250 mg/kg G. lucidum extract produced significant reduction in serum total cholesterol (TC) and low-density cholesterol (LDL-C) contents compared with 500 mg/kg G. lucidum and CQ. Treatment with CQ, however, produced significant reduction in hepatic TC and LDL-C compared with the extract. A dose-dependent significant increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the G. lucidum treated mice compared with normal control but significantly lower compared with CQ-treated mice. Liver HDL-C level was significantly higher in CQ-treated mice compared with normal control and significantly lower compared with G. lucidum-treated and infected untreated mice. A dose-dependent effect of the extract was observed in both serum and liver very-low density lipoprotein cholesterol (VLDL-C). The implication of these results is discussed with respect to the parasite survival and proliferation in the serum and liver.
Retrieval of Parameters for Three-Layer Media with Nonsmooth Interfaces for Subsurface Remote Sensing
Authors: Goykhman Yuriy , Moghaddam Mahta
Published: July 2012

A solution to the inverse problem for a three-layer medium with nonsmooth boundaries, representing a large class of natural subsurface structures, is developed in this paper using simulated radar data. The retrieval of the layered medium parameters is accomplished as a sequential nonlinear optimization starting from the top layer and progressively characterizing the layers below. The optimization process is achieved by an iterative technique built around the solution of the forward scattering problem. The forward scattering process is formulated by using the extended boundary condition method (EBCM) and constructing reflection and transmission matrices for each interface. These matrices are then combined into the generalized scattering matrix for the entire system, from which radar scattering coefficients are then computed. To be efficiently utilized in the inverse problem, the forward scattering model is simulated over a wide range of unknowns to obtain a complete set of subspace-based equivalent closed-form models that relate radar backscattering coefficients to the sought-for parameters including dielectric constants of each layer and separation of the layers. The inversion algorithm is implemented as a modified conjugate-gradient-based nonlinear optimization. It is shown that this technique results in accurate retrieval of surface and subsurface parameters, even in the presence of noise.
Antioxidant and Protective Effects ofBupleurum falcatumon the L-Thyroxine-Induced Hyperthyroidism in Rats
Authors: Kim Seong-Mo , Kim Sang-Chan , Chung In-Kwon , Cheon Woo-Hyun , Ku Sae-Kwang
Published: July 2012

Bupleuri Radix (BR), the dried roots ofBupleurum falcatumL., has been used in folk medicine as an antiinflammatory and antioxidative agent. The aqueous extract of BR was evaluated for its possible ameliorative effect in the regulation of hyperthyroidism in l-thyroxine- (LT4-) induced rat model. After oral administration of 300, 150, and 75 mg/kg of BR extracts, once a day for 15 days from 12th LT4 treatments, changes on the body, thyroid gland, liver, and epididymal fat pad weights, serum triiodothyronine, thyroxine, thyroid-stimulating hormone, asparte aminotransferase and alanine aminotransferase concentrations, hepatic lipid peroxidation, glutathione contents, superoxide dismutase, and catalase activities were investigated with thyroid gland, liver, and epididymal fat histopathological changes. The effects of BR extracts were compared with that of propylthiouracil, a standard antithyroid drug 10 mg/kg (intraperitoneally). In this experiment, BR extracts dose dependently reversed LT4-induced hyperthyroidisms, and these effects indicating their potential in the regulation of hyperthyroidism. Further, the BR extract normalized LT4-induced liver oxidative stresses, and also reduced liver and epididymal fat pad changes. BR extracts 150 mg/kg showed comparable effects on the LT4-induced rat hyperthyroidism as compared with PTU 10 mg/kg. These effects of BR may help the improvement of hyperthyroidisms and accompanied various organ damages.
Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process
Authors: Adamson Catherine S.
Published: July 2012

Protease-mediated maturation of HIV-1 virus particles is essential for virus infectivity. Maturation occurs concomitant with immature virus particle release and is mediated by the viral protease (PR), which sequentially cleaves the Gag and Gag-Pol polyproteins into mature protein domains. Maturation triggers a second assembly event that generates a condensed conical capsid core. The capsid core organizes the viral RNA genome and viral proteins to facilitate viral replication in the next round of infection. The fundamental role of proteolytic maturation in the generation of mature infectious particles has made it an attractive target for therapeutic intervention. Development of small molecules that target the PR active site has been highly successful and nine protease inhibitors (PIs) have been approved for clinical use. This paper provides an overview of their development and clinical use together with a discussion of problems associated with drug resistance. The second-half of the paper discusses a novel class of antiretroviral drug termed maturation inhibitors, which target cleavage sites in Gag not PR itself. The paper focuses on bevirimat (BVM) the first-in-class maturation inhibitor: its mechanism of action and the implications of naturally occurring polymorphisms that confer reduced susceptibility to BVM in phase II clinical trials.
Uncertainty Analysis in Population-Based Disease Microsimulation Models
Authors: Sharif Behnam , Kopec Jacek A. , Wong Hubert , Finès Philippe , Sayre Eric C. , Liu Ran R. , Wolfson Michael C.
Published: July 2012

Objective. Uncertainty analysis (UA) is an important part of simulation model validation. However, literature is imprecise as to how UA should be performed in the context of population-based microsimulation (PMS) models. In this expository paper, we discuss a practical approach to UA for such models.Methods. By adapting common concepts from published UA guidelines, we developed a comprehensive, step-by-step approach to UA in PMS models, including sample size calculation to reduce the computational time. As an illustration, we performed UA for POHEM-OA, a microsimulation model of osteoarthritis (OA) in Canada.Results. The resulting sample size of the simulated population was 500,000 and the number of Monte Carlo (MC) runs was 785 for 12-hour computational time. The estimated 95% uncertainty intervals for the prevalence of OA in Canada in 2021 were 0.09 to 0.18 for men and 0.15 to 0.23 for women. The uncertainty surrounding the sex-specific prevalence of OA increased over time.Conclusion. The proposed approach to UA considers the challenges specific to PMS models, such as selection of parameters and calculation of MC runs and population size to reduce computational burden. Our example of UA shows that the proposed approach is feasible. Estimation of uncertainty intervals should become a standard practice in the reporting of results from PMS models.
Urine Telomerase for Diagnosis and Surveillance of Bladder Cancer
Authors: Lamarca Angela , Barriuso Jorge
Published: July 2012

Bladder cancer has increased incidence during last decades. For those patients with nonmuscle involved tumors, noninvasive diagnosis test and surveillance methods must be designed to avoid current cystoscopies that nowadays are done regularly in a lot of patients. Novel urine biomarkers have been developed during last years. Telomerase is important in cancer biology, improving the division capacity of cancer cells. Even urinary telomerase could be a potentially useful urinary tumor marker; its use for diagnosis of asymptomatic and symptomatic patients or its impact during surveillance is still unknown. Moreover, there will need to be uniformity and standardization in the assays before it can become useful in clinical practice. It does not seem to exist a real difference between the most classical assays for the detection of urine telomerase (TRAP and hTERT). However, the new detection methods with modified TeloTAGGG telomerase or with gold nanoparticles must also be taken into consideration for the correct development of this diagnosis method. Maybe the target population would be the high-risk groups within screening programs. To date there is no enough evidence to use it alone and to eliminate cystoscopies from the diagnosis and surveillance of these patients. The combination with cytology or FISH is still preferred.
A Novel, Sensitive Assay for Behavioral Defects in Parkinson's Disease ModelDrosophila
Authors: Shaltiel-Karyo Ronit , Davidi Dan , Menuchin Yotam , Frenkel-Pinter Moran , Marcus-Kalish Mira , Ringo John , Gazit Ehud , Segal Daniel
Published: July 2012

Parkinson's disease is a common neurodegenerative disorder with the pathology ofα-synuclein aggregation in Lewy bodies. Currently, there is no available therapy that arrests the progression of the disease. Therefore, the need of animal models to followα-synuclein aggregation is crucial.Drosophila melanogasterhas been researched extensively as a good genetic model for the disease, with a cognitive phenotype of defective climbing ability. The assay for climbing ability has been demonstrated as an effective tool for screening new therapeutic agents for Parkinson's disease. However, due to the assay's many limitations, there is a clear need to develop a better behavioral test. Courtship, a stereotyped, ritualized behavior ofDrosophila, involves complex motor and sensory functions in both sexes, which are controlled by large number of neurons; hence, behavior observed during courtship should be sensitive to disease processes in the nervous system. We used a series of traits commonly observed in courtship and an additional behavioral trait—nonsexual encounters—and analyzed them using a data mining tool. We found defective behavior of the Parkinson's model male flies that were tested with virgin females, visible at a much younger age than the climbing defects. We conclude that this is an improved behavioral assay for Parkinson's model flies.
Extracellular Vesicles and Their Convergence with Viral Pathways
Authors: Wurdinger Thomas , Gatson NaTosha N. , Balaj Leonora , Kaur Balveen , Breakefield Xandra O. , Pegtel D. Michiel
Published: July 2012

Extracellular vesicles (microvesicles), such as exosomes and shed microvesicles, contain a variety of molecules including proteins, lipids, and nucleic acids. Microvesicles appear mostly to originate from multivesicular bodies or to bud from the plasma membrane. Here, we review the convergence of microvesicle biogenesis and aspects of viral assembly and release pathways. Herpesviruses and retroviruses, amongst others, recruit several elements from the microvesicle biogenesis pathways for functional virus release. In addition, noninfectious pleiotropic virus-like vesicles can be released, containing viral and cellular components. We highlight the heterogeneity of microvesicle function during viral infection, addressing microvesicles that can either block or enhance infection, or cause immune dysregulation through bystander action in the immune system. Finally, endogenous retrovirus and retrotransposon elements deposited in our genomes millions of years ago can be released from cells within microvesicles, suggestive of a viral origin of the microvesicle system or perhaps of an evolutionary conserved system of virus-vesicle codependence. More research is needed to further elucidate the complex function of the various microvesicles produced during viral infection, possibly revealing new therapeutic intervention strategies.
Cutaneous Manifestations of Systemic Lupus Erythematosus
Authors: Uva Luís , Miguel Diana , Pinheiro Catarina , Freitas João Pedro , Marques Gomes Manuel , Filipe Paulo
Published: July 2012

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. The skin is one of the target organs most variably affected by the disease. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. Cutaneous lesions account for four of these 11 revised criteria of SLE. Skin lesions in patients with lupus may be specific or nonspecific. This paper covers the SLE-specific cutaneous changes: malar rash, discoid rash, photosensitivity, and oral mucosal lesions as well as SLE nonspecific skin manifestations, their pathophysiology, and management. A deeper thorough understanding of the cutaneous manifestations of SLE is essential for diagnosis, prognosis, and efficient management. Thus, dermatologists should cooperate with other specialties to provide optimal care of SLE patient.
Preliminary Results on the Use of Leather Chrome Shavings for Air Passive Sampling
Authors: Sanjuán-Herráez D. , Chabaane L. , Tahiri S. , Pastor A. , de la Guardia M.
Published: July 2012

A new passive sampler based on low-density polyethylene (LDPE) layflat tube filled with chrome shavings from tannery waste residues was evaluated to determine volatile organic compounds (VOCs) in indoor and outdoor areas. VOCs were directly determined by head space-gas chromatography-mass spectrometry (HS-GC-MS) without any pretreatment of the sampler and avoiding the use of solvents. Limit of detection values ranging from 20 to 75 ng sampler−1and good repeatability values were obtained for VOCs under study with relative standard deviation values from 2.8 to 9.6% except for carbon disulfide for which it was 22.5%. The effect of the amount of chrome shavings per sampler was studied and results were compared with those obtained using empty LDPE tubes, to demonstrate the capacity of chrome shavings to adsorb VOCs.
Dynamics of a Transportation Network Model with Homogeneous and Heterogeneous Users
Authors: Li Yingguo , Tan Zhijia , Chen Qiong
Published: July 2012

This paper studies the dynamics of the traveler′s day‐to‐day route adjustment process in the general transportation network with fixed or elastic demand and homogeneous or heterogeneous users. Each traveler is assumed to adjust his/her route choice according to the excess travel cost between the instantaneous experienced travel cost and a certain referred level, which induces an aggregate path flow dynamics. We call the path flow dynamics the excess travel cost dynamics, which corresponds to the excess payoff dynamics in evolutionary games and serves a general framework of modeling the homogeneous or heterogeneous route choice behavior of travelers.
Distribution of Vapor Pressure in the Vacuum Freeze‐Drying Equipment
Authors: Zhang Shiwei , Liu Jun
Published: July 2012

In the big vacuum freeze‐drying equipment, the drying rate of materials is uneven at different positions. This phenomenon can be explained by the uneven distribution of vapor pressure in chamber during the freeze‐drying process. In this paper, a mathematical model is developed to describe the vapor flow in the passageways either between material plates and in the channel between plate groups. The distribution of vapor pressure along flow passageway is given. Two characteristic factors of passageways are defined to express the effects of structural and process parameters on vapor pressure distribution. The affecting factors and their actions are quantitatively discussed in detail. Two examples are calculated and analyzed. The analysis method and the conclusions are useful to estimate the difference of material drying rate at different parts in equipment and to direct the choice of structural and process parameters.
Avoiding Misdiagnosis in Patients with Neurological Emergencies
Authors: Pope Jennifer V. , Edlow Jonathan A.
Published: July 2012

Approximately 5% of patients presenting to emergency departments have neurological symptoms. The most common symptoms or diagnoses include headache, dizziness, back pain, weakness, and seizure disorder. Little is known about the actual misdiagnosis of these patients, which can have disastrous consequences for both the patients and the physicians. This paper reviews the existing literature about the misdiagnosis of neurological emergencies and analyzes the reason behind the misdiagnosis by specific presenting complaint. Our goal is to help emergency physicians and other providers reduce diagnostic error, understand how these errors are made, and improve patient care.
Identification of Active Phase for Selective Oxidation of Benzyl Alcohol with Molecular Oxygen Catalyzed by Copper‐Manganese Oxide Nanoparticles
Authors: Ali Roushown , Adil S. F. , Al-warthan Abdulrahman , Siddiqui M. Rafiq H.
Published: July 2012

Catalytic activity of copper‐manganese mixed oxide nanoparticles (Cu/Mn = 1 : 2) prepared by coprecipitation method has been studied for selective oxidation of benzyl alcohol using molecular oxygen as an oxidizing agent. The copper‐manganese (CuMn2) oxide catalyst exhibited high specific activity of 15.04 mmolg−1 h−1 in oxidation of benzyl alcohol in toluene as solvent. A 100% conversion of the benzyl alcohol was achieved with >99% selectivity to benzaldehyde within a short reaction period at 102°C. It was found that the catalytic performance is dependent on calcination temperature, and best activity was obtained for the catalyst calcined at 300°C. The high catalytic performance of the catalyst can be attributed to the formation of active MnO2 phase or absence of less active Mn2O3 phase in the mixed CuMn2 oxide. The catalyst has been characterized by powder X‐ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer Emmett‐Teller (BET) surface area measurement, and Fourier transform infrared (FT‐IR) spectroscopies.
Phase IB Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women with Hormone Receptor–Negative Breast Cancer
Authors: Crew Katherine D. , Brown Powel , Greenlee Heather , Bevers Therese B. , Arun Banu , Hudis Clifford , McArthur Heather L. , Chang Jenny , Rimawi Mothaffar , Vornik Lana , Cornelison Terri L. , Wang Antai , Hibshoosh Hanina , Ahmed Aqeel , Terry Mary Beth , Santella Regina M. , Lippman Scott M. , Hershman Dawn L.
Published: July 2012

Epidemiologic data support an inverse association between green tea intake and breast cancer risk, and numerous experimental studies have shown the antitumor effects of its main component, epigallocatechin gallate (EGCG). We conducted a phase IB dose escalation trial in women with a history of stage I to III hormone receptor–negative breast cancer of an oral green tea extract, polyphenon E (Poly E) 400, 600, 800 twice daily or matching placebo for 6 months. The primary endpoint was to determine the maximum tolerated dose (MTD), defined as the dose that causes 25% dose-limiting toxicity (DLT, grade ≥II). Assignment to dose level was based upon an adaptive design, the continual reassessment method. A mammogram and random core biopsy of the contralateral breast were obtained at baseline and 6 months and serial blood/urine collections every 2 months for biomarker analyses. Forty women were randomized: 10 to placebo, 30 to Poly E (16 at 400 mg, 11 at 600 mg, 3 at 800 mg). There was one DLT at 400 mg (grade III rectal bleeding), three DLTs at 600 mg (grade II weight gain, grade III indigestion and insomnia), and one DLT at 800 mg (grade III liver function abnormality). The DLT rate at 600 mg was 27% (3 of 11). Pharmacologic levels of total urinary tea polyphenols were achieved with all three dose levels of Poly E. Using a novel phase I trial design, we determined the MTD for Poly E to be 600 mg twice daily. This study highlights the importance of assessing toxicity for any chemopreventive agent being developed for chronic use in healthy individuals. Cancer Prev Res; 5(9); 1144–54. ©2012 AACR.
Fine-Needle Aspiration Cytology of Hyalinizing Trabecular Adenoma of the Thyroid in a Patient with Hashimoto’s Thyroiditis: A Case Report
Authors: You Tack Kune , Jang Kyu Yun , Moon Woo Sung , Chung Myoung Ja , Kang Myoung Jae , Lee Dong Geun , Park Ho Sung
Published: July 2012

Background: Hyalinizing trabecular adenoma (HTA) is a rare benign epithelial tumor of the thyroid which shows a prominent trabecular growth pattern and stromal hyalinization. On fine-needle aspiration cytology, HTA is frequently misdiagnosed as either papillary thyroid carcinoma (PTC) or medullary carcinoma. We present both the cytologic and the histopathologic features of HTA in a patient with Hashimoto’s thyroiditis. Case: Cytologically, the tumor cells showed a low nucleocytoplasmic ratio and eccentrically located nuclei, nuclear grooves, and eosinophilic pseudoinclusions. Lymphocyte-dominant inflammatory cells were present in the background, raising the possibility of thyroiditis. Histologically, the tumor was a 0.5 × 0.4 cm-sized mass and showed a trabecular and nested pattern of tumor cells separated by scant hyaline material in the background of Hashimoto’s thyroiditis. Tumor cells showed abundant eosinophilic granular cytoplasms, nuclear grooves, and pseudoinclusions, as well as immunoreactivity for MIB-1 on the cell membrane. We diagnosed this lesion as HTA in a patient with Hashimoto’s thyroiditis. Conclusion: Although distinction of HTA from PTC in the cytologic specimen is difficult, especially in cases associated with Hashimoto’s thyroiditis, cohesive cell aggregates with a low nucleocytoplasmic ratio and eccentrically located nuclei may be helpful to consider the possibility of HTA.
Importance of the Residual Volume of the Cytological Solution for the Reproducibility of the Hybrid Capture 2 High-Risk Human Papillomavirus DNA Test
Authors: Catteau Xavier , Vanhaeverbeek Michel , Noël Jean-Christophe
Published: July 2012

Objective: Human papillomavirus (HPV) infections are widespread in all human populations, and a large number of studies have demonstrated a relationship between high-risk (HR)-HPV infections and cervical intraepithelial neoplasia or invasive cervical cancer. To the best of our knowledge, no independent study clearly demonstrates the importance of the quantity of residual liquid after cytology in terms of sensitivity for HR-HPV detection. Study Design: We conducted a study to assess the relationship between the liquid-based cytology volume and the sensitivity of the hybrid capture 2 test for the detection of HR-HPV in 23 cytological high-grade squamous intraepithelial lesions with a cervical intraepithelial neoplasia grade 2 or worse protocol on biopsy. Results: Although the sensitivity of the tests showed no statistically significant differences, we still found a significant variation in the median values of relative light units/control according to the amount of liquid used. Conclusions: If 2 ml of liquid is used, this could lead to false negatives when the value of relative light units/control is only slightly greater than 1. The fact that we found a lower viral load at 2 versus 4 or 8 ml was also important in terms of predicting the evolution of cervical lesions. We recommend using at least 4 ml of the PreservCyt solution for HR-HPV detection with the hybrid capture 2 test.
The Significance of Hyperkeratosis in Pap Smears with Squamous Intraepithelial Lesion
Authors: Izadi-Mood Narges , Sarmadi Soheila , Alijani Sorour , Sanii Sara
Published: July 2012

Objective: It was the aim of this study to evaluate the significance of reporting hyperkeratosis in cervical smears. Study Design: Cervicovaginal smears with low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), prepared from 2004 to 2007, were retrospectively reviewed. Anucleated squamous cells were counted. The smears were classified into two groups, based on the presence of <2 or ≥2 clusters of anucleated cells, and then compared. Results: Sixty Pap smears showing SILs (34 LSILs and 26 HSILs) as well as 120 random satisfactory smears without squamous or glandular abnormalities were selected. A statistically significant difference was found between the SIL group and the control group regarding the mean number of hyperkeratotic clusters (2.8 in the SIL and 1.9 in the control group; p = 0.012). Moreover, the mean number of hyperkeratotic clusters (3.3 in the LSIL and 2.2 in the HSIL group) had a statistically significant correlation with the diagnosis of the lesion as LSIL or HSIL (p = 0.0006). Conclusion: Our findings suggest that hyperkeratosis in the form of ≥2 clusters of anucleated squamous cells could be an indicator of underlying LSIL.
Decompressive Surgery for Malignant Middle Cerebral Artery Infarcts: The Results of Randomized Trials Can Be Reproduced in Daily Practice
Authors: Lucas Christian , Thines Laurent , Dumont Frédéric , Leclerc Xavier , Riegel Bernard , Cordonnier Charlotte , Fourrier François , Hénon Hilde , Rousseaux Marc , Leys Didier , Lejeune Jean-Paul
Published: July 2012

Background: In clinical randomized controlled trials (RCTs), decompressive surgery (DS) for malignant middle cerebral artery (MMCA) infarcts leads to a 50% absolute risk reduction in mortality, and improves the 1-year functional outcome. The reproducibility of these results in routine practice has never been evaluated. The purpose of this study was to test the hypothesis that the results of DS for MMCA in practice are similar to those observed in the surgical group of RCTs. Methods: We prospectively included the first 31 patients who underwent DS for MMCA. They were screened based on similar criteria as in the meta-analysis. The primary outcome was a modified Rankin Scale (mRS) score of ≤4, and secondary outcomes were mRS of ≤3 and death at 1 year. Results: Thirty-one patients underwent DS for MMCA. The 1-year mRS was ≤4 in 22 patients (71.0%) and ≤3 in 16 (51.6%). Seven patients died (22.6%). Conclusion: This observational study showed that DS for MMCA in a center without previous experience provides similar results as those obtained in the surgical arm of RCTs.
A Comparison of Liquid-Based Cytology with Conventional Cytology in Cervical Cancer Screening
Authors: Akamatsu Setsu , Kodama Shoji , Himeji Yukari , Ikuta Naomi , Shimagaki Nikako
Published: July 2012

Objective: To clarify the performance of liquid-based cytology (LBC) and conventional methods of preparing cervical specimens for cytological screening. Study Design: We studied 236,511 patients who participated in a population-based cervical cancer screening program conducted in the Niigata prefecture between 2005 and 2008. The percentage of unsatisfactory specimens and the disease detection rate were compared between specimens prepared by LBC and conventional methods. Results: (1) The LBC method demonstrated a significantly lower percentage of unsatisfactory specimens than the conventional method (1.38 and 11.45%, respectively; p < 0.01). (2) Among the initial women, tumor lesions were detected in 0.57% of those examined with the LBC method, which was significantly higher than the positivity rate of those examined with the conventional method (0.25%; p < 0.05). Among the women with repeat screening, disease was detected in 0.08% of those examined with LBC twice, which was significantly lower than the positivity rates for those examined with the conventional method followed by the LBC method (0.11%) or the conventional method twice (0.16%; p < 0.05). Conclusion: The LBC method is significantly more useful than the conventional method in terms of the low adequacy rate and the high detection rate of cancer in cervical cancer screening in a localized area in Japan.
A Comparative Study of 3-Week and 6-Week Duration of Double-J Stent Placement in Renal Transplant Recipients
Authors: Huang Liting , Wang Xiaoxia , Ma Yujie , Wang Jin , Tao Xiaoqin , Liao Lianming , Tan Jianming
Published: July 2012

Purpose: To compare the efficiency and safety of 3-week and 6-week duration of double-J stent placement in patients who received a kidney transplant. Patients and Methods: Post-transplant recipients were divided into two groups. The duration of double-J stent placement was 6 weeks in group 1 (n = 186) and 3 weeks in group 2 (n = 179). Both groups received similar antibiotics and immunosuppressants. The double-J stents were removed cystoscopically under local anesthesia. The patients were followed up for at least 3 months. Urological complications were recorded, including urinary leakage, obstruction, and urinary tract infections. Results: There were no severe urological complications in both groups. Duration of 3 weeks was as effective as 6 weeks in preventing urological complications such as urinary leak and stenoses. There was no significant difference between the two groups in average duration of macroscopic hematuria, incidents of malposition of double-J stent and calculus formation in or around the stent. Compared with group 1, patients in group 2 had a lower incidence of urinary irritation and fewer urinary tract infection episodes. Conclusions: A shorter duration of double-J stent placement in renal transplantation recipients does not increase urological complications. In addition, it may decrease urinary tract infection and urinary irritation.
The Effects of the Selective Cyclooxygenase-2 Inhibitor on Endometrial Cytological Findings in Uterine Endometrial Cancer Patients
Authors: Hasegawa Kiyoshi , Kawamura Kyoko , Kato Rina , Komiyama Shinichi , Kaneko Chiyuki , Udagawa Yasuhiro
Published: July 2012

Objective: We previously reported that oral administration of the selective cyclooxygenase-2 (COX-2) inhibitor etodolac results in antitumor effects in endometrial cancer tissue. Herein, we investigated whether these antitumor effects could be assessed using endometrial cytological findings. Study Design: Etodolac (400 mg b.i.d. for 2 weeks) was administered preoperatively to 21 endometrial cancer patients: 16 had COX-2-positive disease and 5 had COX-2-negative disease. Twenty-one pairs of pre- and post-etodolac-treatment endometrial cytological samples were collected to review changes in the cytological features. Results: In the COX-2-positive patients, nuclear atypia was slightly decreased in 3 of the 16 cases, while the mitotic index was decreased in all cases. Cellular overlapping and tumor cell cluster outlines were somewhat affected in 6 and 8 cases, respectively. Nuclear/cytoplasmic ratio, anisokaryosis and hyperchromasia were also reduced in 6, 4, and 2 cases, respectively; however, tumor diathesis and nucleoli features were unchanged. In contrast, endometrial cytological features did not appear to be affected in the 5 COX-2-negative patients. Conclusions: We conclude that the antitumor effects observed in endometrial cancer tissues following oral administration of etodolac are reflected in and can be easily assessed by evaluating endometrial cytological features.
Subclassification of Non-Small Cell Lung Cancer by Cytologic Sampling: A Logical Approach with Selective Use of Immunocytochemistry
Authors: Kimbrell Hillary Z. , Gustafson Karen S. , Huang Min , Ehya Hormoz
Published: July 2012

Objectives: To determine the diagnostic accuracy of cytomorphology for subclassifying non-small cell lung cancer into adenocarcinoma (AC) and squamous cell carcinoma (SqC), and the utility of immunocytochemistry (ICC) for poorly differentiated cases. Study Design: Preoperative cytologic diagnoses of SqC, AC, or non-small cell carcinoma (NSCC) were compared with surgical resection diagnoses. NSCC cases with adequate cell block material were stained with CK7, CK5/6, TTF-1 and p63 antibodies and subclassified as SqC, AC, or equivocal. Results: 123 of 140 (88%) preoperative cytologic specimens had a malignant diagnosis, including 36 SqC, 72 AC, 6 adenosquamous carcinomas (ASC), and 9 large cell carcinomas (LCC). Accurate cytologic diagnoses were rendered in 18 (50%) SqC and 49 (68%) AC; 26 of 54 cases with a diagnosis of NSCC had adequate cell block material for ICC. TTF-1 and p63 accurately classified 8 of 9 (89%) SqC and 8 of 8 (100%) AC. One SqC, 2 ASC and 3 LCC had equivocal staining, while 1 ASC and 3 LCC stained as AC. Conclusions: The majority of SqC and AC (56%) can be classified by cytomorphology alone. TTF-1 and p63 ICC on cell blocks can provide accurate subclassification for NSCC in the vast majority of cases.
Cytotechnologist On-Site Evaluation of Pancreas Fine Needle Aspiration Adequacy: Comparison with Cytopathologists and Correlation with the Final Interpretation
Authors: Olson Matthew T. , Ali Syed Z.
Published: July 2012

Objective: To compare on-site evaluations of adequacy (OSEA) of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) of the pancreas performed by cytotechnologists and cytopathologists. Study Design: A 10-year retrospective review of 2,426 OSEA from 2,223 procedures in 1,984 patients was performed. Adequacy statistics were calculated along with the accuracy of the OSEA for each OSEA provider. The effect of other variables, including the lifetime number of EUS pancreatic OSEA, the number of years of experience at the time of each case, the institutional number of EUS FNA, and the number of smears was evaluated with ANOVA. Results: There was no difference in the adequacy downgrade rate for cytotechnologists versus cytopathologists during this study period (38.2 vs. 32.2%, p = 0.13). Neither individual cytologist experience with EUS-guided pancreatic FNA (p = 0.25) nor years in practice (p = 0.86) was correlated with the accuracy of the OSEA. The experience of the institution with EUS-guided pancreatic FNA was correlated with both adequacy (p = 0.003) and accuracy (p = 0.000001). Conclusion: Cytotechnologists and cytopathologists are comparably accurate in OSEA of EUS-guided pancreatic FNA. The adequacy and accuracy of the OSEA increase with institutional experience, and this increase is not solely attributable to cytologist factors.
On-Site Toluidine Blue Staining and Screening Improves Efficiency of Fine-Needle Aspiration Cytology Reporting
Authors: Ammanagi A.S. , Dombale V.D. , Patil Sharada S.
Published: July 2012

Objective: We investigated the role of on-site toluidine blue staining and screening in fine-needle aspiration cytology (FNAC) reporting for patients with thyroid nodules, palpable breast lumps and palpable lymph nodes. Study Design: A total of 200 consecutive patients with a palpable lymph node or a lump in the breast or thyroid referred to the outpatient department for FNAC were included in this study. We used toluidine blue to stain FNAC slides for the evaluation of smear adequacy. The toluidine blue-stained slides were compared with the same slides after being decolorised and Papanacolaou (PAP)-stained. Results: Out of 200 cases, 28 (14%) were deemed unsatisfactory on the first attempt as assessed by rapid staining. These included 16 (38%) of 42 thyroid cases, 10 (10.4%) of 96 breast lump cases and 2 (3.2%) of 62 lymph node cases. A repeat FNAC in the same sitting on these 28 patients showed adequate material in 24 (12%) of them. Therefore, for 98%, a decision could be made at the very first visit to plan further management. Conclusions: We concluded that toluidine blue offers excellent cytological details for the preliminary identification of the lesion and to decide on the adequacy of the material for definitive diagnosis on FNAC slides.