bluuebunny/crossref_metadata_2025 huggingface dataset:
Subconjunctival Bevacizumab Injection in Glaucoma Filtering Surgery: A Case Control Series
Authors: Wang Jing , Harasymowycz Paul
Published: March 2013

Aims. To describe the use of subconjunctival bevacizumab (SCB) injection in the combined cataract and glaucoma filtering surgery (GFS). Methods. Retrospective comparative case series. Thirty eyes of twenty-eight patients who had GFS followed by SCB injection as part of post-operative management were included (Group SCB). The types of GFS included trabeculectomy and non-penetrating glaucoma surgery (NPGS) with mitomycin-C. Outcome measures included the reduction of intraocular pressure (IOP) and medications. Age-matched patients who had the same types of surgery without SCB were selected as a control group (Group C). Results. The types of GFS were: combined cataract surgery and NPGS (SCB: 20; C: 24), phacotrabeculectomy (SCB: 6; C: 3), NPGS (SCB: 3; C: 2) and trabeculectomy alone (SCB: 1; C: 1). The average follow-up time was 16.9 (±8.2) months in the SCB group and 19.6 (±11.5) months in the controls. 1.25 mg of bevacizumab was injected on average 14.1 (range: 3–42) days post-GFS. The mean IOP decreased from 21.9 (±9.8) to 11.9 (±4.7) mmHg in the controls and from 19.6 (±8.9) to 14.0 (±4.7) mmHg in the SCB group. There was no statistically significant difference between the two groups (P=0.11). Complications included three cases of branch vein occlusion in the SCB group. Conclusions. SCB did not result in better outcome in term of IOP reduction. Clinicians should monitor its side effects in glaucoma patients.
Modeling and Optimization of Inventory-Distribution Routing Problem for Agriculture Products Supply Chain
Authors: Liao Li , Li Jianfeng , Wu Yaohua
Published: March 2013

Mathematical models of inventory-distribution routing problem for two-echelon agriculture products distribution network are established, which are based on two management modes, franchise chain and regular chain, one-to-many, interval periodic order, demand depending on inventory, deteriorating treatment cost of agriculture products, start-up costs of vehicles and so forth. Then, a heuristic adaptive genetic algorithm is presented for the model of franchise chain. For the regular chain model, a two-layer genetic algorithm based on oddment modification is proposed, in which the upper layer is to determine the distribution period and quantity and the lower layer is to seek the optimal order cycle, quantity, distribution routes, and the rational oddment modification number for the distributor. By simulation experiments, the validity of the algorithms is demonstrated, and the two management modes are compared.
A Subwavelength Plasmonic Waveguide Filter with a Ring Resonator
Authors: Zhai Xiang , Wen Shuangchun , Xiang Dong , Wang Ling-Ling , Rexidaiguli Wujiaihemaiti , Wang Liu , Fan Dianyun
Published: March 2013

The transmission characteristics of the electromagnetic wave are numerically investigated in two‐dimensional compound plasmonic structures composed of two straight subwavelength metal‐insulator‐metal (MIM) waveguides and a ring resonator. The two straight MIM waveguides situate on both sides of the ring resonator, and the MIM waveguide of the outgoing side has a positional angular deviation θ relative to the MIM waveguide of the incoming side. The results show that the filtering performances of the asymmetric structures (θ ≠ 0∘) are greatly improved in comparison with the symmetric structure (θ = 0∘). For most of the asymmetric structures, there is a transmission minimum at the slightly bigger wavelength than one at which the transmission peak appears for the symmetric structures, and there is still a transmission peak at the wavelength of the transmission peak of the symmetric structures. Moreover, the difference between the transmission peak and valley is increased, and the breadth of the transmission peak becomes narrow.
Improved Thermally Grown Oxide Scale in Air Plasma Sprayed NiCrAlY/Nano‐YSZ Coatings
Authors: Daroonparvar Mohammadreza , Azizi Mat Yajid Muhamad , Yusof Noordin Mohd , Sakhawat Hussain Mohammad
Published: March 2013

Oxidation has been considered as one of the principal disruptive factors in thermal barrier coating systems during service. So, oxidation behavior of thermal barrier coating (TBC) systems with nanostructured and microstructured YSZ coatings was investigated at 1000∘C for 24 h, 48 h, and 120 h. Air plasma sprayed nano‐YSZ coating exhibited a trimodal structure. Microstructural characterization also demonstrated an improved thermally grown oxide scale containing lower spinels in nano‐TBC system after 120 h of oxidation. This phenomenon is mainly related to the unique structure of the nano‐YSZ coating, which acted as a strong barrier for oxygen diffusion into the TBC system at elevated temperatures. Nearly continues but thinner Al2O3 layer formation at the NiCrAlY/nano‐YSZ interface was seen, due to lower oxygen infiltration into the system. Under this condition, spinels formation and growth on the Al2O3 oxide scale were diminished in nano‐TBC system compared to normal TBC system.
Gold Nanoparticles and Nanocomposites in Clinical Diagnostics Using Electrochemical Methods
Authors: Chandra Pranjal , Singh Jai , Singh Amardeep , Srivastava Ananya , Goyal Rajendra N. , Shim Yoon Bo
Published: March 2013

Progress and development in clinical diagnostics certainly focus upon the advances in the nanomaterials, particularly gold nanoparticles (AuNPs) that offer promise to solve the biocompatible and sensitive detection systems. This paper focuses on the recent application of AuNPs in clinical diagnosis. Various important methods of AuNPs synthesis and their application in clinical detection of various biomolecules using electrochemical detection methods have been described. AuNPs alone and in various composites are also described based on the various biosensors design recently published for the detection of cancer biomarkers, proteins, bacteria, and cancer cells. The effect of AuNPs type and size in clinical detection has also been briefly illustrated.
Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach
Authors: Kumar Alok , Ghosh Devlina , Singh R. L.
Published: March 2013

Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients.
Lavender and the Nervous System
Authors: Koulivand Peir Hossein , Khaleghi Ghadiri Maryam , Gorji Ali
Published: March 2013

Lavender is traditionally alleged to have a variety of therapeutic and curative properties, ranging from inducing relaxation to treating parasitic infections, burns, insect bites, and spasm. There is growing evidence suggesting that lavender oil may be an effective medicament in treatment of several neurological disorders. Several animal and human investigations suggest anxiolytic, mood stabilizer, sedative, analgesic, and anticonvulsive and neuroprotective properties for lavender. These studies raised the possibility of revival of lavender therapeutic efficacy in neurological disorders. In this paper, a survey on current experimental and clinical state of knowledge about the effect of lavender on the nervous system is given.
Transfer Matrix Method for the Determination of the Natural Vibration Characteristics of Realistic Thrusting Launch Vehicle—Part I
Authors: Abbas Laith K. , Min-Jiao Li , Xiao-Ting Rui
Published: March 2013

The feasibility of using the transfer matrix method (TMM) to compute the natural vibration characteristics of a flexible rocket/satellite launch vehicle is explored theoretically. In the approach to the problem, a nonuniform free-free Timoshenko and Euler-Bernoulli beamlike structure is modeled. A provision is made to take into consideration the effects of shear deformation and rotary inertia. Large thrust-to-weight ratio leads to large axial accelerations that result in an axial inertia load distribution from nose to tail which causes the development of significant compressive forces along the length of the launch vehicle. Therefore, it is important to take into account this effect in the transverse vibration model. Once the transfer matrix of a single component has been obtained, the product of all component matrices composes the matrix of the entire structure. The frequency equation and mode shape are formulated in terms of the elements of the structural matrices. Flight test and analytical results validate the present TMM formulas.
Eighteen-Month-Old Infants Generalize to Analog Props across a Two-Week Retention Interval in an Elicited Imitation Paradigm
Authors: Kingo Osman S. , Krøjgaard Peter
Published: March 2013

We report a generalization experiment in which 72 18-month-old infants were tested in the elicited imitation paradigm. Two questions were addressed: (1) whether infants' were able to generalize to differently looking (shape and color changes) but functionally equivalent props and (2) whether narrative support at both encoding and retrieval would facilitate memory. The results revealed that the 18-month-old infants were indeed capable of generalizing to differently looking but functionally equivalent props across a retention interval of two weeks. However, contrary to expectations, narrative support did not facilitate memory or generalization.
Molecular Dynamics of Film Formation of Metal Tetrasulfonated Phthalocyanine and Poly Amidoamine Dendrimers
Authors: Silva L. G. , Neto A. M. J. C. , Gaffo L. , Borges R. S. , Ramalho Teodorico C. , Machado Nélio
Published: March 2013

We performed molecular dynamics computer simulations to elucidate the behavior and properties of the metal tetrasulfonated phthalocyanine molecule and the poly(amidoamine) dendrimers in self‐assembly depositions, respectively, on poly(allylamine hydrochloride) polymer and on film formed by metal tetrasulfonated phthalocyanine with poly(allylamine hydrochloride). Important physical properties of phthalocyanines were obtained such as the kinetic energy and temperature in situ. By the semiempirical model, we also obtained the UV‐Vis absorption spectrum of the film formed by cobalt tetrasulfonated phthalocyanine deposited on poly(allylamine hydrochloride). We performed a study with poly(amidoamine) dendrimers on their deposition time on metal tetrasulfonated phthalocyanine, poly(allylamine hydrochloride) film, and we show the relationship of deposition time with the electrical charge and molecular mass of phthalocyanines. The deposition times of the dendrimers, as a function of their mass, were also elucidated.
In Vivo Characterization of a Novel -Secretase Inhibitor SCH 697466 in Rodents and Investigation of Strategies for Managing Notch-Related Side Effects
Authors: Hyde Lynn A. , Zhang Qi , Del Vecchio Robert A. , Leach Prescott T. , Cohen-Williams Mary E. , Chen Lei , Wong Gwendolyn T. , McHugh Nansie A. , Chen Joseph , Higgins Guy A. , Asberom Theodros , Li Wei , Pissarnitski Dmitri , Levitan Diane , Nomeir Amin A. , Clader John W. , Zhang Lili , Parker Eric M.
Published: March 2013

Substantial evidence implicates -amyloid (A) peptides in the etiology of Alzheimer’s disease (AD). A is produced by the proteolytic cleavage of the amyloid precursor protein by - and -secretase suggesting that -secretase inhibition may provide therapeutic benefit for AD. Although many -secretase inhibitors have been shown to be potent at lowering A, some have also been shown to have side effects following repeated administration. All of these side effects can be attributed to altered Notch signaling, another -secretase substrate. Here we describe the in vivo characterization of the novel -secretase inhibitor SCH 697466 in rodents. Although SCH 697466 was effective at lowering A, Notch-related side effects in the intestine and thymus were observed following subchronic administration at doses that provided sustained and complete lowering of A. However, additional studies revealed that both partial but sustained lowering of Aand complete but less sustained lowering of A were successful approaches for managing Notch-related side effects. Further, changes in several Notch-related biomarkers paralleled the side effect observations. Taken together, these studies demonstrated that, by carefully varying the extent and duration of A lowering by -secretase inhibitors, it is possible to obtain robust and sustained lowering of A without evidence of Notch-related side effects.
CHD1 Is a 5q21 Tumor Suppressor Required for ERG Rearrangement in Prostate Cancer
Authors: Burkhardt Lia , Fuchs Sarah , Krohn Antje , Masser Sawinee , Mader Malte , Kluth Martina , Bachmann Frederik , Huland Hartwig , Steuber Thomas , Graefen Markus , Schlomm Thorsten , Minner Sarah , Sauter Guido , Sirma Hüseyin , Simon Ronald
Published: March 2013

Deletions involving the chromosomal band 5q21 are among the most frequent alterations in prostate cancer. Using single-nucleotide polymorphism (SNP) arrays, we mapped a 1.3 megabase minimally deleted region including only the repulsive guidance molecule B (RGMB) and chromodomain helicase DNA-binding protein 1 (CHD1) genes. Functional analyses showed that CHD1 is an essential tumor suppressor. FISH analysis of 2,093 prostate cancers revealed a strong association between CHD1 deletion, prostate-specific antigen (PSA) biochemical failure (P = 0.0038), and absence of ERG fusion (P < 0.0001). We found that inactivation of CHD1 in vitro prevents formation of ERG rearrangements due to impairment of androgen receptor (AR)-dependent transcription, a prerequisite for ERG translocation. CHD1 is required for efficient recruitment of AR to responsive promoters and regulates expression of known AR-responsive tumor suppressor genes, including NKX3-1, FOXO1, and PPARγ. Our study establishes CHD1 as the 5q21 tumor suppressor gene in prostate cancer and shows a key role of this chromatin remodeling factor in prostate cancer biology. Cancer Res; 73(9); 2795–805. ©2013 AACR.
Center of Cancer Systems Biology Second Annual Workshop—Tumor Metronomics: Timing and Dose Level Dynamics
Authors: Hahnfeldt Philip , Hlatky Lynn , Klement Giannoula Lakka
Published: March 2013

Metronomic chemotherapy, the delivery of doses in a low, regular manner so as to avoid toxic side effects, was introduced over 12 years ago in the face of substantial clinical and preclinical evidence supporting its tumor-suppressive capability. It constituted a marked departure from the classic maximum-tolerated dose (MTD) strategy, which, given its goal of rapid eradication, uses dosing sufficiently intense to require rest periods between cycles to limit toxicity. Even so, upfront tumor eradication is frequently not achieved with MTD, whereupon a de facto goal of longer-term tumor control is often pursued. As metronomic dosing has shown tumor control capability, even for cancers that have become resistant to the same drug delivered under MTD, the question arises whether it may be a preferable alternative dosing approach from the outset. To date, however, our knowledge of the coupled dynamics underlying metronomic dosing is neither sufficiently well developed nor widely enough disseminated to establish its actual potential. Meeting organizers thus felt the time was right, armed with new quantitative approaches, to call a workshop on “Tumor Metronomics: Timing and Dose Level Dynamics” to explore prospects for gaining a deeper, systems-level appreciation of the metronomics concept. The workshop proved to be a forum in which experts from the clinical, biologic, mathematical, and computational realms could work together to clarify the principles and underpinnings of metronomics. Among other things, the need for significant shifts in thinking regarding endpoints to be used as clinical standards of therapeutic progress was recognized. Cancer Res; 73(10); 2949–54. ©2013 AACR.
Molecular Profiling of Aromatase Inhibitor–Treated Postmenopausal Breast Tumors Identifies Immune-Related Correlates of Resistance
Authors: Dunbier Anita K. , Ghazoui Zara , Anderson Helen , Salter Janine , Nerurkar Ashutosh , Osin Peter , A'hern Roger , Miller William R. , Smith Ian E. , Dowsett Mitch
Published: March 2013

Purpose: Estrogen withdrawal by treatment with aromatase inhibitors is the most effective form of endocrine therapy for postmenopausal estrogen receptor–positive (ER+) breast cancer. However, response to therapy varies markedly and understanding of the precise molecular effects of aromatase inhibitors and causes of resistance is limited. We aimed to identify in clinical breast cancer those genes and pathways most associated with resistance to aromatase inhibitors by examining the global transcriptional effects of AI treatment.

Experimental Design: Baseline and 2-week posttreatment biopsies were obtained from 112 postmenopausal women with ER+ breast cancer receiving neoadjuvant anastrozole. Gene expression data were obtained from 81 baseline and 2-week paired samples. Pathway analysis identified (i) the most prevalent changes in expression and (ii) the pretreatment genes/pathways most related to poor antiproliferative response.

Results: A total of 1,327 genes were differentially expressed after 2-week treatment (false discovery rate < 0.01). Proliferation-associated genes and classical estrogen-dependent genes were strongly downregulated whereas collagens and chemokines were upregulated. Pretreatment expression of an inflammatory signature correlated with antiproliferative response to anastrozole and this observation was validated in an independent study. Higher expression of immune-related genes such as SLAMF8 and TNF as well as lymphocytic infiltration were associated with poorer response (P < 0.001) and validated in an independent cohort.

Conclusions: The molecular response to aromatase inhibitor treatment varies greatly between patients consistent with the variable clinical benefit from aromatase inhibitor treatment. Higher baseline expression of an inflammatory signature is associated with poor antiproliferative response and should be assessed further as a novel biomarker and potential target for aromatase inhibitor-treated patients. Clin Cancer Res; 19(10); 2775–86. ©2013 AACR.
FGFR2 Gene Amplification in Gastric Cancer Predicts Sensitivity to the Selective FGFR Inhibitor AZD4547
Authors: Xie Liang , Su Xinying , Zhang Lin , Yin Xiaolu , Tang Lili , Zhang Xiuhua , Xu Yanping , Gao Zeren , Liu Kunji , Zhou Minhua , Gao Beirong , Shen Danping , Zhang Lianhai , Ji Jiafu , Gavine Paul R. , Zhang Jingchuan , Kilgour Elaine , Zhang Xiaolin , Ji Qunsheng
Published: March 2013

Purpose: FGFR gene aberrations are associated with tumor growth and survival. We explored the role of FGFR2 amplification in gastric cancer and the therapeutic potential of AZD4547, a potent and selective ATP-competitive receptor tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR)1–3, in patients with FGFR2-amplified gastric cancer.

Experimental Design: Array-comparative genomic hybridization and FISH were used to identify FGFR2 amplification in gastric cancer patient tumor samples. The effects of FGFR2 modulation were investigated in gastric cancer cells with FGFR2 amplification and in patient-derived gastric cancer xenograft (PDGCX) models using two approaches: inhibition with AZD4547 and short hairpin RNA (shRNA) knockdown of FGFR2.

Results: Amplification of the FGFR2 gene was identified in a subset of Chinese and Caucasian patients with gastric cancer. Gastric cancer cell lines SNU-16 and KATOIII, carrying the amplified FGFR2 gene, were extremely sensitive to AZD4547 in vitro with GI50 values of 3 and 5 nmol/L, respectively. AZD4547 effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules and induced apoptosis in SNU-16 cells. Furthermore, inhibition of FGFR2 signaling by AZD4547 resulted in significant dose-dependent tumor growth inhibition in FGFR2-amplified xenograft (SNU-16) and PDGCX models (SGC083) but not in nonamplified models. shRNA knockdown of FGFR2 similarly inhibited tumor growth in vitro and in vivo. Finally, compared with monotherapy, we showed enhancement of in vivo antitumor efficacy using AZD4547 in combination with chemotherapeutic agents.

Conclusion: FGFR2 pathway activation is required for driving growth and survival of gastric cancer carrying FGFR2 gene amplification both in vitro and in vivo. Our data support therapeutic intervention with FGFR inhibitors, such as AZD4547, in patients with gastric cancer carrying FGFR2 gene amplification. Clin Cancer Res; 19(9); 2572–83. ©2013 AACR.
The HSP90 Inhibitor NVP-AUY922 Potently Inhibits Non–Small Cell Lung Cancer Growth
Authors: Garon Edward B. , Finn Richard S. , Hamidi Habib , Dering Judy , Pitts Sharon , Kamranpour Naeimeh , Desai Amrita J. , Hosmer Wylie , Ide Susan , Avsar Emin , Jensen Michael Rugaard , Quadt Cornelia , Liu Manway , Dubinett Steven M. , Slamon Dennis J.
Published: March 2013

Heat shock protein 90 (HSP90) is involved in protein folding and functions as a chaperone for numerous client proteins, many of which are important in non–small cell lung cancer (NSCLC) pathogenesis. We sought to define preclinical effects of the HSP90 inhibitor NVP-AUY922 and identify predictors of response. We assessed in vitro effects of NVP-AUY922 on proliferation and protein expression in NSCLC cell lines. We evaluated gene expression changes induced by NVP-AUY922 exposure. Xenograft models were evaluated for tumor control and biological effects. NVP-AUY922 potently inhibited in vitro growth in all 41 NSCLC cell lines evaluated with IC50 < 100 nmol/L. IC100 (complete inhibition of proliferation) < 40 nmol/L was seen in 36 of 41 lines. Consistent gene expression changes after NVP-AUY922 exposure involved a wide range of cellular functions, including consistently decreased dihydrofolate reductase after exposure. NVP-AUY922 slowed growth of A549 (KRAS-mutant) xenografts and achieved tumor stability and decreased EGF receptor (EGFR) protein expression in H1975 xenografts, a model harboring a sensitizing and a resistance mutation for EGFR-tyrosine kinase inhibitors in the EGFR gene. These data will help inform the evaluation of correlative data from a recently completed phase II NSCLC trial and a planned phase IB trial of NVP-AUY922 in combination with pemetrexed in NSCLCs. Mol Cancer Ther; 12(6); 890–900. ©2013 AACR.
Waiting for Platelet Counts Causes Unsubstantiated Delay of Thrombolysis Therapy
Authors: Breuer L. , Huttner H.B. , Kiphuth I.C. , Ringwald J. , Hilz M.J. , Schwab S. , Köhrmann M.
Published: March 2013

Background: Platelet counts (PCs) <100,000/µl are considered as a contraindication for intravenous thrombolysis (IVT). While US guidelines recommend IVT initiation before the availability of clotting tests, the guidelines of the European Stroke Organization give no such practical advice. We aimed to assess the incidence of thrombocytopenia in IVT patients, outcome after thrombolysis in affected patients and the time gained by initiating treatment prior to availability of PC results. Methods: All patients with thrombocytopenia were identified in our prospectively acquired thrombolysis database. Baseline demographic data, intracerebral hemorrhage rates as well as functional outcome were assessed. The median time between initiation of thrombolysis and availability of PCs was calculated. Results: Of 625 IVT patients, 3 (0.5%) had thrombocytopenia at stroke onset. None of them developed intracerebral hemorrhage (ICH) or died during the follow-up. Waiting for PCs would have delayed treatment in 72.4% of the patients, with a median hypothetical delay of 22 min (interquartile range: 11–41 min). Conclusions: To date, there are no sufficient data to evaluate the ICH risk in thrombocytopenic patients. However, thrombocytopenia is rare in IVT patients. Thus, generally waiting for PC results prior to initiation of IVT is not warranted. Avoiding this significant delay yields shorter door-to-needle times and potentially more effective treatment.
Safety and Immunogenicity of a DNA Vaccine Encoding Human Calcium-Activated Chloride Channel 1 (hCLCA1) in Asthmatic Mice
Authors: Song L.Q. , Li Y. , Li W.N. , Zhang W. , Qi H.W. , Wu C.G.
Published: March 2013

Background: Calcium-activated chloride channels (CLCAs) have been found to be preferentially expressed on the secretory epithelium. They may play a pivotal role in mucous overproduction by bronchial goblet cells in asthma. It has been reported that the inhibition of CLCAs with niflumic acid could relieve the symptoms of asthma. However, niflumic acid has serious adverse effects. DNA vaccination is considered to be a promising strategy to treat allergic diseases such as asthma and dust mite allergy. Methods: We constructed a vaccine encoding human CLCA1 (hCLCA1) and evaluated its effects on promoting antibodies against hCLCA1 and the related preventive function in a mouse model of asthma. Results: Our results reveal that the induced hCLCA1 antibodies can be detected in the first 2 weeks after immunization with hCLCA1 plasmids (hCLCA1-p) by intramuscular injection and augmented gradually in the following several weeks. The autoantibodies against hCLCA1 induced by the DNA vaccine bound to three segments of the mouse CLCA3 (mCLCA3) protein, including the amino terminal (PepN), the carboxyl terminal (PepC) and the middle of the protein (PepM). In our study, mice immunized with hCLCA1-p developed fewer pathological changes compared with other control groups, including a remarkable reduction in the air pressure-time index of the trachea, the number of eosinophils and mast cells in the bronchoalveolar lavage fluid and the mRNA level of MUC5AC in goblet cells. Conclusion: Taken together, our results suggest that a DNA vaccine encoding the CLCA protein may have potential as a useful pharmacotherapy for asthma in the future.
Administration of Yellow Fever Vaccine in Patients with Egg Allergy
Authors: Rutkowski K. , Ewan P.W. , Nasser S.M.
Published: March 2013

Background: The population of large parts of Africa, South America and travellers to these areas are at risk of yellow fever (YF) with a 50% mortality risk. Yellow fever vaccine (YFV) propagated in hens' eggs confers protection in 95% of the vaccinated. The rate of anaphylaxis for YFV ranges from 0.42 to 1.8/100,000 doses with most cases considered to be due to egg allergy. Egg allergy is a contraindication for the YFV. Nevertheless, the potential fatal sequelae from YF give the incentive to protect everyone at risk irrespective of their allergic status. Methods: Six subjects who had had a recent reaction to egg and who were travelling to endemic areas (3 adults and 3 children) underwent skin prick tests (SPT) with undiluted YFV and egg extract. Intradermal tests for YFV were undertaken at a 1:10 dilution. In 4 egg-allergic patients with a positive SPT to YFV, a 7-step desensitization protocol was used. A 2-step (10 + 90%) protocol was used in the 2 subjects with a negative YFV SPT. Premedication was not administered. Results: All 6 patients were successfully vaccinated. Four patients completed desensitization: 1 developed mild local erythema at the injection site, 1 had fleeting generalized urticaria with local erythema/angioedema and 2 did not experience any adverse reactions. Patients who received YFV in 2 steps developed no adverse reactions. Conclusions: We describe the successful administration of YFV in 6 egg-allergic patients. The Cambridge Allergy 7-step protocol allows for its safe administration in patients with positive SPT to YFV. A 2-step protocol can be used in patients with negative YFV SPT.
Quality of Nuchal Translucency Measurements Correlates with Broader Aspects of Program Rigor and Culture of Excellence
Authors: Evans Mark I. , Krantz David A. , Hallahan Terrence , Sherwin John , Britt David W.
Published: March 2013

Introduction: To determine if nuchal translucency (NT) quality correlates with the extent to which clinics vary in rigor and quality control. Methods: We correlated NT performance quality (bias and precision) of 246,000 patients with two alternative measures of clinic culture - % of cases for whom nasal bone (NB) measurements were performed and % of requisitions correctly filled for race-ethnicity and weight. Results: When requisition errors occurred in <5% of cases, the average MoM (multiple of the median) was 0.97. When >5% (33%), the curve lowered to 0.93 MoM (p < 0.001) with both bias and precision of measurements impaired. Likewise, for centers with NB >90%, MoM was 0.99 compared to those <10% at 0.93 (p < 0.001). Precision and bias were highly correlated (p < 0.001). Conclusions: Rigor in NT measurements has improved, but the discussion has been confined to individuals. Progressive educational and remediation strategies need to expand to a second dimension - clinics themselves. Cross-clinic variation in NT quality exists independent of individual variation in NT quality, and two divergent indices of program rigor are associated with NT quality. Quality control must be program wide, and to effect continued improvement in the quality of NT results across time, the cultures of clinics must become a target for intervention.
New Food Allergies in a European Non-Mediterranean Region: Is Cannabis sativa to Blame?
Authors: Ebo D.G. , Swerts S. , Sabato V. , Hagendorens M.M. , Bridts C.H. , Jorens P.G. , De Clerck L.S.
Published: March 2013

Background: Allergy to fruit and vegetables exhibit geographic variation regarding the severity of symptoms and depending on the sensitization profile of the patient. These sensitization profiles and routes remain incompletely understood. Cannabis is a very popular drug and derived from Cannabis sativa, a plant containing lipid transfer proteins (LTP) also known as important allergens in plant and fruit allergies. In this study we sought to elucidate a potential connection between C. sativa allergy and plant food allergies. Methods: A case-control study involving 21 patients consulting for plant food allergies. Twelve patients were cannabis allergic and 9 had a pollen or latex allergy without cannabis allergy. Testing for cannabis IgE implied measurement of specific IgE, skin testing and basophil activation tests. Allergen component analysis was performed with a microarray technique. Results: Plant food allergy in patients with documented cannabis allergy had more severe reactions than patients without cannabis allergy and frequently implied fruits and vegetables that are not observed in a (birch) pollen-related food syndrome. With the exception of 1 patient with cannabis allergy, all were sensitized to nonspecific (ns)-LTP. Conclusion: Our data suggest that illicit cannabis abuse can result in cannabis allergy with sensitization to ns-LTP. This sensitization might result in various plant-food allergies. Additional collaborative studies in different geographical areas are needed to further elucidate on this hypothesis.
A Giant Adrenal Pseudocyst Mimicking an Adrenal Cancer: Case Report and Review of the Literature
Authors: Passoni S. , Regusci L. , Peloni G. , Brenna M. , Fasolini F.
Published: March 2013

Adrenal pseudocysts are rare lesions that develop within the adrenal glands, generally from vessel ectasia or from degenerative adenomas or hematomas. They are usually non-functional and asymptomatic. The reported potential malignant transformation of an adrenal cyst is ca. 7% and indicates radical excision of these masses. We report the case of a 69-year-old man with hypertension, chronic obstructive pulmonary disease, and obesity in whom microscopic hematuria was detected during a routine examination performed by his family doctor. To investigate the cause of this microscopic hematuria, the patient underwent computed tomography of the abdomen, which showed a well-defined 12-cm lesion of the left adrenal gland with calcification and necrotic components that was compressing the left kidney, pancreas, and spleen. Suspecting adrenal carcinoma, after preoperative staging, a left subcostal laparotomy was performed, with resection of the left adrenal gland, a splenectomy, and resection of the pancreatic tail. The histology showed an adrenal pseudocyst with a fibrous capsule containing amorphous eosinophilic material with calcification and cholesterol crystals. The patient's postoperative course was uneventful, and he was discharged 12 days after surgery.
Erich Harnack (1852–1915) and a Short History of Apomorphine
Authors: Taba Pille , Lees Andrew , Stern Gerald
Published: March 2013

Apomorphine, now established as an efficacious therapy for refractory motor fluctuations in levodopa-treated Parkinson’s disease, has a long and chequered history in medical and veterinary therapeutics. The preclinical in vivo pharmacological effects of apomorphine were first studied about 150 years ago following which the drug was introduced for the treatment of behavioural vices in domesticated animals. Erich Harnack’s early pharmacological studies in Dorpat (now Tartu, Estonia), where he belonged to the pharmacological dynasty of Buchheim and Schmiedeberg, are of particular historical significance as he emphasised that while apomorphine had potent emetic effects, the drug also had complex effects on the central nervous system.
Parameters Associated with Chronic Spontaneous Urticaria Duration and Severity: A Systematic Review
Authors: Rabelo-Filardi Rafael , Daltro-Oliveira Renato , Campos Régis A.
Published: March 2013

Background: Although some authors have already evaluated the predictive value of various parameters regarding the duration of chronic spontaneous urticaria (CSU), it remains uncertain which ones have importance in clinical practice as prognostic factors that indeed enable prediction. Similarly, some authors have investigated parameters that might be related to severe cases of CSU. However, the results of studies evaluating several parameters as markers of disease severity are fragmented. Thus, we performed a systematic review to summarize the findings of studies investigating the parameters associated with CSU duration and severity. Methods: Two authors independently searched PubMed until June 2012 for observational retrospective or prospective studies addressing clinical or laboratory parameters associated with disease duration or severity in CSU patients. Results: We found 1,136 potentially relevant published papers related to the subject, 34 of which were included in the systematic review. A total of 16, 6 and 12 articles evaluated CSU parameters on severity, duration or both, respectively. Conclusions: Our findings suggest that disease severity might predict CSU duration. Similarly, evidence suggests that plasma levels of prothrombin fragment 1 + 2, D-dimer and C-reactive protein may function as markers of CSU severity.
Hereditary Hemorrhagic Telangiectasia: Breakpoint Characterization of a Novel Large Deletion in ACVRL1 Suggests the Causing Mechanism
Authors: Boeri Laura , Radi Orietta , Canzonieri Cecilia , Buscarini Elisabetta , Scatigno Agnese , Minelli Antonella , Ornati Federica , Pagella Fabio , Danesino Cesare , Olivieri Carla
Published: March 2013

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Mutations in either ENG or ACVRL1 account for around 85% of cases, and 10% are large deletions and duplications. Here we present a large novel deletion in ACVRL1 gene and its molecular characterization in a 3 generation Italian family. We employed short tandem repeats (STRs) analysis, direct sequencing, multiplex ligation-dependant probe amplification (MLPA) analysis, and ‘deletion-specific' PCR methods. STRs Analysis at ENG and ACVRL1 loci suggested a positive linkage for ACVRL1. Direct sequencing of this gene did not identify any mutations, while MLPA identified a large deletion. These results were confirmed and exactly characterized with a ‘deletion-specific' PCR: the deletion size is 4,594 bp and breakpoints in exon 3 and intron 8 show the presence of short direct repeats of 7 bp [GCCCCAC]. We hypothesize, as causative molecular mechanism, the replication slippage model. Understanding the fine mechanisms associated with genomic rearrangements may indicate the nonrandomness of these events, highlighting hot spots regions. The complete concordance among MLPA, STRs analysis and ‘deletion-specific PCR' supports the usefulness of MLPA in HHT molecular analysis.
Rapamycin Inhibits Smooth Muscle Cell Proliferation and Obstructive Arteriopathy Attributable to Elastin Deficiency
Authors: Li Wei , Li Qingle , Qin Lingfeng , Ali Rahmat , Qyang Yibing , Tassabehji May , Pober Barbara R. , Sessa William C. , Giordano Frank J. , Tellides George
Published: March 2013

Objective—

Patients with elastin deficiency attributable to gene mutation (supravalvular aortic stenosis) or chromosomal microdeletion (Williams syndrome) are characterized by obstructive arteriopathy resulting from excessive smooth muscle cell (SMC) proliferation, mural expansion, and inadequate vessel size. We investigated whether rapamycin, an inhibitor of the cell growth regulator mammalian target of rapamycin (mTOR) and effective against other SMC proliferative disorders, is of therapeutic benefit in experimental models of elastin deficiency.

Approach and Results—

As previously reported,
Eln
−/−
mice demonstrated SMC hyperplasia and severe stenosis of the aorta, whereas
Eln
+/−
mice exhibited a smaller diameter aorta with more numerous but thinner elastic lamellae. Increased mTOR signaling was detected in elastin-deficient aortas of newborn pups that was inhibited by maternal administration of rapamycin. mTOR inhibition reduced SMC proliferation and aortic obstruction in
Eln
−/−
pups and prevented medial hyperlamellation in
Eln
+/−
weanlings without compromising aortic size. However, rapamycin did not prolong the survival of
Eln
−/−
pups, and it retarded the somatic growth of juvenile
Eln
+/−
and
Eln
+/+
mice. In cell cultures, rapamycin inhibited prolonged mTOR activation and enhanced proliferation of SMC derived from patients with supravalvular aortic stenosis and with Williams syndrome.

Conclusions—

mTOR inhibition may represent a pharmacological strategy to treat diffuse arteriopathy resulting from elastin deficiency.
Long-Chain Monounsaturated Fatty Acids and Incidence of Congestive Heart Failure in 2 Prospective Cohorts
Authors: Imamura Fumiaki , Lemaitre Rozenn N. , King Irena B. , Song Xiaoling , Steffen Lyn M. , Folsom Aaron R. , Siscovick David S. , Mozaffarian Dariush
Published: March 2013

Background—

Decades-old animal experiments suggested that dietary long-chain monounsaturated fatty acids (LCMUFAs) caused cardiotoxicity, leading, for example, development of Canola oil (Canadian oil low in erucic acid) from rapeseed. However, potential cardiotoxicity in humans and contemporary dietary sources of LCMUFAs are unknown.

Methods and Results—

We prospectively investigated the associations of plasma phospholipid LCMUFAs (20:1, 22:1, and 24:1), assessed as objective biomarkers of exposure, with incidence congestive heart failure in 2 independent cohorts: 3694 older adults (mean age, 75.2±5.2 years) in the Cardiovascular Health Study (CHS; 1992–2006) and 3577 middle-aged adults (mean age, 54.1±5.8 years) in the Atherosclerosis Risk in Communities Study, Minnesota subcohort (ARIC; 1987–2008). We further examined dietary correlates of circulating LCMUFAs in CHS and ARIC and US dietary sources of LCMUFAs in the 2003–2010 National Health and Nutrition Examination Survey (NHANES). In CHS, 997 congestive heart failure events occurred during 39 238 person-years; in ARIC, 330 events congestive heart failure events occurred during 64 438 person-years. After multivariable adjustment, higher levels of 22:1 and 24:1 were positively associated with greater incident congestive heart failure in both CHS and ARIC; hazard ratios were 1.34 (95% confidence interval, 1.02–1.76) and 1.57 (95% confidence interval, 1.11–2.23) for highest versus lowest quintiles of 22:1, respectively, and 1.75 (95% confidence interval, 1.23–2.50) and 1.92 (95% confidence interval, 1.22–3.03) for 24:1, respectively (
P
for trend ≤0.03 each). A variety of foods were related to circulating LCMUFAs in CHS and ARIC, consistent with food sources of LCMUFAs in NHANES, including fish, poultry, meats, whole grains, and mustard.

Conclusions—

Higher circulating levels of 22:1 and 24:1, with apparently diverse dietary sources, were associated with incident congestive heart failure in 2 independent cohorts, suggesting possible cardiotoxicity of LCMUFAs in humans.
Cerebral Microbleeds and Recurrent Stroke Risk
Authors: Charidimou Andreas , Kakar Puneet , Fox Zoe , Werring David J.
Published: March 2013

Background and Purpose—

To evaluate cerebral microbleeds (CMBs) and future stroke risk (including intracerebral hemorrhage [ICH]) in patients with ischemic stroke (IS) or transient ischemic attack.

Materials and Methods—

A systematic review and meta-analysis of prospective cohorts with recent IS/transient ischemic attack. We critically appraised studies and calculated pooled odds ratios (ORs), using the Mantel–Haenszel fixed-effects method, for ICH or recurrent IS, in patients with versus without CMBs.

Results—

We pooled data from 10 cohorts, including 3067 patients. CMBs were associated with a significant increased risk of any recurrent stroke (OR, 2.25; 95% confidence interval [95% CI], 1.70–2.98;
P
<0.0001), ICH (OR, 8.52; 95%CI, 4.23–17.18;
P
=0.007), and IS (OR, 1.55; 95%CI, 1.12–2.13;
P
<0.0001). When stratified by study population ethnicity (Asian versus Western [mainly white European]), the association of CMBs with ICH was significant for Asian cohorts (5 studies; n=1915; OR, 10.43; 95%CI, 4.59–23.72;
P
<0.0001) but borderline and of lower magnitude for Western cohorts (4 studies; n=885; OR, 3.87; 95%CI, 0.91–16.4;
P
=0.066). By contrast, there was a significant association of CMBs with recurrent IS in Western (3 studies; n=899) but not Asian cohorts (4 studies; n=1357; OR, 2.23; 95%CI, 1.29–3.85;
P
=0.004 compared with OR, 1.30; 95%CI, 0.88–1.93;
P
=0.192, respectively).

Conclusions—

There is consistent evidence of an increased risk of recurrent stroke after IS or transient ischemic attack in patients with CMBs. The risk for spontaneous ICH appears to be greater than the risk for recurrent IS. Our findings also suggest that the balance of risk for ICH versus IS differs between Asian and Western cohorts.
Characterization of Arterial Thrombus Composition by Magnetic Resonance Imaging in a Swine Stroke Model
Authors: Fujimoto Motoaki , Salamon Noriko , Mayor Fernando , Yuki Ichiro , Takemoto Koichiro , Vinters Harry V. , Viñuela Fernando
Published: March 2013

Background and Purpose—

The aim of this study is to analyze the histological composition of acute arterial thrombi and their MRI signals.

Methods—

Two different types of experimental thrombi, erythrocyte- and fibrin-rich thrombus, were created and injected into an experimentally formed stenotic common carotid artery in swine. MRI of the in vivo and in vitro samples was obtained immediately after the thrombus application.

Results—

Erythrocyte component showed high on fluid-attenuated inversion recovery, and iso on T2-weighted signal in both in vitro and in vivo. Fibrin-rich thrombus was composed of fibrin/platelet and nucleated cell layers, which demonstrated iso- and low intensities, respectively, in both fluid-attenuated inversion recovery and T2-weighted images in vitro. Mixed signal was obtained in vivo.

Conclusions—

We successfully characterized the only erythrocyte component of acute thrombus by MRI.
Reduction in Distal Emboli With Proximal Flow Control During Mechanical Thrombectomy
Authors: Chueh Ju-Yu , Kühn Anna Luisa , Puri Ajit S. , Wilson Scott D. , Wakhloo Ajay K. , Gounis Matthew J.
Published: March 2013

Background and Purpose—

To evaluate the impact of proximal flow control on efficacy and safety of mechanical thrombectomy in an in vitro middle cerebral artery occlusion.

Methods—

Three independent variables, including clot type, device (Merci Retriever, Solitaire FR, and Trevo devices), and use of a balloon guide catheter, were used to ascertain the impact of proximal flow control on the size and number of distal emboli generated during thrombectomy. Secondary end points were the recanalization rate and amount of flow restored.

Results—

Use of the balloon guide catheter during thrombectomy of the fragile, hard clot significantly reduced the formation of large distal emboli with a diameter >1 mm, regardless of the device used (
P
<0.01). Applying aspiration via the balloon guide catheter in place of the conventional guide catheter resulted in a significant increase of flow reversal (
P
<0.0001). Prior to thrombectomy, deployment of the stent-trievers produced immediate flow restoration through the soft and hard clot occlusions, 69.2±27.3 and 45.5±22.8 mL/min, respectively, that was preserved after the balloon inflation because of collateral flow via the posterior communication artery. After deployment but before thrombectomy, no flow was restored when using the Merci Retriever. After thrombectomy, complete flow restoration was achieved in a majority of cases. The Merci Retriever required more thrombectomy attempts to achieve hard clot removal compared with the stent-trievers when the conventional guide catheter was used (1.5 versus 1.1).

Conclusions—

The risk of distal embolization was significantly reduced with the use of the balloon guide catheter.
Is Navigation in Virtual Reality with fMRI Really Navigation?
Authors: Taube Jeffrey S. , Valerio Stephane , Yoder Ryan M.
Published: March 2013

Identifying the neural mechanisms underlying spatial orientation and navigation has long posed a challenge for researchers. Multiple approaches incorporating a variety of techniques and animal models have been used to address this issue. More recently, virtual navigation has become a popular tool for understanding navigational processes. Although combining this technique with functional imaging can provide important information on many aspects of spatial navigation, it is important to recognize some of the limitations these techniques have for gaining a complete understanding of the neural mechanisms of navigation. Foremost among these is that, when participants perform a virtual navigation task in a scanner, they are lying motionless in a supine position while viewing a video monitor. Here, we provide evidence that spatial orientation and navigation rely to a large extent on locomotion and its accompanying activation of motor, vestibular, and proprioceptive systems. Researchers should therefore consider the impact on the absence of these motion-based systems when interpreting virtual navigation/functional imaging experiments to achieve a more accurate understanding of the mechanisms underlying navigation.