bluuebunny/crossref_metadata_2025 huggingface dataset:
NOS3 894G>T Polymorphism is Associated With Progression of Kidney Disease and Cardiovascular Morbidity in Type 2 Diabetic Patients: NOS3 as a Modifier Gene for Diabetic Nephropathy?
Authors: Kuricová Katarína , Tanhäuserová Veronika , Pácal Lukáš , Bartáková Vendula , Brožová Lucie , Jarkovský Jiří , Kaňková Kateřina
Published: March 2014

Background/Aims: We have previously associated SNP 894G>T in the NOS3 gene with diabetic nephropathy (DN) using multi-locus analysis. Variant 894G>T has been widely studied as a DN susceptibility factor with contradictory results. In the present study we genotyped 894G>T in the cohort of prospectively followed type 2 diabetics with the aim to investigate its possible role in the progression of DN and development of morbidity and mortality associated with diabetes. Methods: 311 subjects with defined stage of DN were enrolled in the study and followed up for a median of 38 months. We considered three end-points: progression of DN, major cardiovascular event and all-cause mortality. Results: Considering baseline GFR, age at enrolment and diabetes duration as confounders, Cox regression analysis identified 894GT genotype as a risk factor for DN progression (HR = 1.843 [95% CI 1.088 - 3.119], P = 0.023) and 894TT genotype as a risk factor for major cardiovascular event (HR = 2.515 [95% CI 1.060 - 5.965], P = 0.036). Conclusion: We ascertained the significant effect of the NOS3 894G>T variant on DN progression and occurrence of major cardiovascular event in T2DM subjects. Based on these results NOS3 can be considered a modifier gene for DN.
Evaluating the Use of Prostate-Specific Antigen as an Instrument for Early Detection of Prostate Cancer beyond Urologists: Results of a Representative Cross-Sectional Questionnaire Study of General Practitioners and Internal Specialists
Authors: Gilfrich Christian , May Matthias , Braun Kay-Patrick , Lebentrau Steffen , Lehsnau Mike , Ecke Thorsten , Schmailzl Kurt J.G. , Al-Dumaini Salah , Hallmann Steffen , Ahmed Ali M. , Maurer Julia , Karl Thomas , Braun Vittoria , Haferkamp Axel , Brookman-May Sabine , Bauer Ricarda M. , Stief Christian G. , Hoschke Bernd , Maurer Odilo , Wolff Ingmar
Published: March 2014

Objectives: The aim of this cross-sectional study was to evaluate the value of prostate-specific antigen (PSA) testing as a tool for early detection of prostate cancer (PCa) applied by general practitioners (GPs) and internal specialists (ISs) as well as to assess criteria leading to the application of PSA-based early PCa detection. Methods: Between May and December 2012, a questionnaire containing 16 items was sent to 600 GPs and ISs in the federal state Brandenburg and in Berlin (Germany). The independent influence of several criteria on the decision of GPs and ISs to apply PSA-based early PCa detection was assessed by multivariate logistic regression analysis (MLRA). Results: 392 evaluable questionnaires were collected (return rate 65%). 81% of the physicians declared that they apply PSA testing for early PCa detection; of these, 58 and 15% would screen patients until the age of 80 and 90 years, respectively. In case of a pathological PSA level, 77% would immediately refer the patient to a urologist, while 13% would re-assess elevated PSA levels after 3-12 months. Based on MLRA, the following criteria were independently associated with a positive attitude towards PSA-based early PCa detection: specialisation (application of early detection more frequent for GPs and hospital-based ISs) (OR 3.12; p < 0.001), physicians who use exclusively GP or IS education (OR 3.95; p = 0.002), and physicians who recommend yearly PSA assessment after the age of 50 (OR 6.85; p < 0.001). Conclusions: GPs and ISs frequently apply PSA-based early PCa detection. In doing so, 13% would initiate specific referral to a urologist in case of pathological PSA values too late. Improvement of this situation could possibly result from specific educational activities for non-urological physicians active in fields of urological core capabilities, which should be guided by joint boards of the national associations of urology and general medicine.
FADD Is Upregulated in Relapsing Remitting Multiple Sclerosis
Authors: Reuss Reinhard , Mistarz Marta , Mirau Andreas , Kraus Jörg , Bödeker Rolf-Hasso , Oschmann Patrick
Published: March 2014

Objective: To elucidate the role of tumor necrosis factor (TNF) receptor signal transduction in multiple sclerosis (MS). Methods: We performed a cross-sectional analysis of the gene expression of TNF receptor-associated death domain protein (TRADD) and Fas-associated death domain protein (FADD) in peripheral blood leukocytes of 23 relapsing remitting (RR), 19 secondary progressive (SP) and 12 primary progressive (PP) MS patients, as well as of 29 healthy controls by quantitative RT-PCR. Additionally, we monitored a subgroup of 15 RR MS patients longitudinally every 3 months over the time period of 9 months. Results: FADD expression was significantly elevated in RR MS patients compared to the other disease courses (p < 0.048). The median of FADD expression was elevated in the RR MS patient groups compared to the healthy group, but this was not significant (p < 0.053). The median of TRADD expression was elevated in the patient groups compared to the healthy group, but this was not significant (p < 0.14). Neither variable changed significantly over the time course of 9 months. Conclusion: FADD elevation in leukocytes might be interpreted as the molecular equivalent of an elevated general inflammatory activity in RR MS patients compared to other disease courses. FADD elevation in RR MS reinforces the concept that different pathophysiological and immunological processes sustain RR MS and SP or PP MS.
Tamoxifen Treatment for Pubertal Gynecomastia in Two Siblings with Partial Androgen Insensitivity Syndrome
Authors: Saito Reiko , Yamamoto Yukiyo , Goto Motohide , Araki Shunsuke , Kubo Kazuyasu , Kawagoe Rinko , Kawada Yasusada , Kusuhara Koichi , Igarashi Maki , Fukami Maki
Published: March 2014

Background: Although tamoxifen has been shown to be fairly safe and effective for idiopathic pubertal gynecomastia, it remains unknown whether it is also beneficial for gynecomastia associated with endocrine disorders. Here, we report the effect of tamoxifen on pubertal gynecomastia in 2 siblings with partial androgen insensitivity syndrome (PAIS). Case Reports: Cases 1 and 2 presented with persistent pubertal gynecomastia at 13 and 16 years of age, respectively. Physical examinations revealed breast of Tanner stage 3 and normal male-type external genitalia in both cases. Clinical features such as female-type pubic hair and borderline small testis indicated mildly impaired masculinization. Results: Molecular analysis identified a previously reported p.Arg789Ser mutation in the androgen receptor gene (AR) in the 2 cases. Two months of oral administration of tamoxifen ameliorated gynecomastia to Tanner stage 2 with no adverse events. Additional treatment with testosterone enanthate showed negligible effects on body hair and penile length. Hormone values of the 2 cases during tamoxifen treatment remained similar to those in previously reported untreated patients with PAIS. Conclusion: The results indicate that tamoxifen was effective in treating pubertal gynecomastia in these 2 patients with PAIS and may be considered as a therapeutic option in this situation pending further studies.
Postoperative Pulmonary Complications after Surgery in Patients with Interstitial Lung Disease
Authors: Choi Sun Mi , Lee Jinwoo , Park Young Sik , Cho Young-Jae , Lee Chang-Hoon , Lee Sang-Min , Yoon Ho Il , Yim Jae-Joon , Lee Jae Ho , Yoo Chul-Gyu , Lee Choon-Taek , Kim Young Whan , Park Jong Sun
Published: March 2014

Background: Patients with interstitial lung disease (ILD) have a high incidence of postoperative pulmonary complications (PPCs) after lung resection, but there is little data about these complications in ILD after other types of surgery. Objectives: The aim of this study was to examine the characteristics and predictors of PPCs after major surgery in patients with ILD. Methods: We included 336 patients with ILD who underwent major surgery between January 2005 and December 2010 at two tertiary hospitals in Korea. All types of surgery that had been performed under general anesthesia were included. Demographic characteristics, preoperative lung function, and operative conditions including anesthesia time and estimated blood loss were compared between patients with and without PPCs. Results: PPCs occurred in 37 patients (11%). Thirteen patients developed pneumonia, the most common PPC, and 11 had acute exacerbation of ILD. In multivariable analysis, BMI <23 (OR = 2.488, 95% CI: 1.084-5.710, p = 0.031), emergency surgery (OR = 23.992, 95% CI: 2.629-218.949, p = 0.005), lung surgery (OR = 5.090, 95% CI: 1.391-18.628, p = 0.014), and longer anesthesia time (OR = 1.595, 95% CI: 1.143-2.227, p = 0.006) were statistically significant risk factors. Conclusions: The incidence of PPCs detected over all surgeries was not as high as that reported for lung surgery alone in ILD patients. Lower BMI, emergency surgery, lung surgery, and longer anesthesia time were risk factors. Operative conditions as well as lung function should be considered in preoperative planning and management for ILD patients undergoing major surgery.
Distinct Features in the Clinical Presentations of Eosinophilic Esophagitis in Children and Adults: Is This the Same Disease?
Authors: Gonsalves Nirmala
Published: March 2014

Recent consensus guidelines define eosinophilic esophagitis (EoE) as a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Adults with EoE typically present with dysphagia, food impaction and reflux symptoms, while children primarily present with refractory reflux, abdominal pain, vomiting and growth failure. Endoscopic features are also somewhat different in adults and children. Adult patients often present with fibrostenotic features of EoE including rings, strictures and narrow-caliber esophagus, while children present with inflammatory features of EoE including edema, white exudates and furrowing. Despite these differences in symptom and endoscopic presentation, many similarities exist between the two groups suggesting that this is the same disease in both children and adults. First, atopic history and genetic predisposition have been demonstrated in both groups. Most convincing is that both adults and children respond to food allergen avoidance, implicating a common etiology in the pathogenesis of this disease. While additional data is needed to better understand the natural history of EoE, preliminary data suggests that EoE is the same disease in adults and children, but with different phenotypic presentations.
The Complex Relationship between Eosinophilic Esophagitis and Gastroesophageal Reflux Disease
Authors: Katzka David A.
Published: March 2014

That gastroesophageal reflux and eosinophilic esophagitis (EoE) may both lead to esophageal eosinophilia is well known. What is not known is how, if at all, these entities interact to contribute to this pathologic entity in specific patients and how often they occur in patients as synergistic contributors to the disease as opposed to distinct processes. There are several hypotheses by which gastroesophageal reflux disease (GERD) and EoE might interact to cause esophageal eosinophilia. These include (1) reflux of food from the stomach with increased antigenic exposure to esophageal epithelium; (2) reflux-induced dilation of intercellular spaces in the epithelium facilitating dendritic cell and antigen movement through the mucosa, and (3) a common inflammatory pathway activated by both GERD and EoE. Although these hypotheses appear plausible, supporting clinical data is not readily available. For example, it is unclear if the beneficial effect of proton pump inhibitors on esophageal eosinophilia is mediated through control of acid exposure to esophageal mucosa or independent anti-inflammatory effects. There is also a lack of definitive evidence to support an increased incidence of GERD in the pediatric population in the absence of evident risk factors such as obesity. One would think if GERD were an important cofactor in this disease, the incidence of GERD would rise similarly to EoE. It is speculated that GERD and EoE coexist and in some patients interact to facilitate esophageal eosinophilia and its sequelae. However, the presence and degree of this interaction likely varies remarkably. Their presence could be influenced by other factors such as age of the patient and genetic predisposition to EoE.
Diagnostic and Therapeutic Challenges in Pediatric Eosinophilic Esophagitis: Past, Present and Future
Authors: Gupta Sandeep K.
Published: March 2014

In this paper, we will discuss the nuances of pediatric eosinophilic esophagitis based on symptoms, diagnostics and therapy. The diagnostics will include endoscopy, histology and anesthesia. Therapeutics will include the diet, drugs and ‘distress'. Future directions in terms of clinical presentation and diagnostics will be discussed and important issues such as repeated exposure to anesthetic agents and effects of therapy on growth and psychological distress will be listed.
Eosinophilic Esophagitis: Indications for Treatment
Authors: Straumann Alex
Published: March 2014

At present, it is still debated whether the focus of treatment in eosinophilic esophagitis (EoE) should be directed toward a symptomatic or histological response, or even toward a combination of both. This question cannot be answered as long as we have no solid data evaluating the long-term consequences of untreated symptoms and untreated inflammation. Nevertheless, today there are at least three established reasons to treat patients with clinically and histologically active EoE. First, dysphagia has a substantial negative impact on the patient's daily life. Despite the fact that patients often cope with this symptom and accept even marked restrictions in their nutritional habits, they usually experience a marked enhancement in quality of life under treatment. Second, untreated EoE harbors the risk of long-lasting food impactions. There is evidence that this unpleasant, unforeseeable and even risky incident can be prevented by efficient treatment of the eosinophilic inflammation. Third, it has been demonstrated in several clinical studies as well as in animal models that unbridled eosinophilic inflammation leads to a so-called remodeling of the esophagus with wall thickening, stiffness of the organ and stricture. Prevention of esophageal damage caused by tissue remodeling is therefore another reason to strongly advocate a consequential treatment. Finally, there is increasing evidence that untreated EoE might be a risk factor for acute infection of the esophagus with herpes simplex virus (HSV), leading to a severe ulcerative and extremely painful esophagitis. Prevention of HSV esophagitis might therefore be a fourth indication for treating EoE.
Treatment of Adult Eosinophilic Esophagitis with Diet
Authors: Lucendo Alfredo J. , Arias Angel
Published: March 2014

Background/Aims: A growing body of research indicates that dietary therapy is an effective treatment option for children with eosinophilic esophagitis (EoE). Its ability to achieve sustained symptomatic and histological responses is comparable to that of topical steroids, but avoids their use and side effects. Recent studies also support dietary therapy as a preferred treatment option for adult patients. Methods: A comprehensive literature review was carried out to assess the efficacy of the most commonly used dietary interventions in inducing and maintaining disease remission in adult EoE patients as compared with results from pediatric studies. Results: The only available study assessing exclusive feeding with an elemental diet carried out in adults demonstrated a 94% disease remission rate, comparable to the high efficacy reported in pediatric studies. The major drawbacks of this therapy are poor adherence and a rapid disease recurrence after resumption of a normal diet. Although there is limited data on skin allergy testing-directed food elimination in adult patients, the highest efficacy rates observed do not exceed 26% histological remission. Prospective studies on empirical six-food elimination diets in adults provided efficacy rates comparable to those reported in children, achieving disease remission in approximately 75% of patients. However, specific food triggers can only be identified after documented recurrence of eosinophilic inflammation as determined with repeated endoscopic biopsies. Prolonged avoidance of the offending food(s) produces sustained remission of adult EoE. Conclusions: Diet is a feasible therapeutic option for adult EoE patients, providing them with the same effective drug-free alternative as in pediatric patients.
Evaluation of Allergic Conjunctivitis by Thermography
Authors: Hara Yuko , Shiraishi Atsushi , Yamaguchi Masahiko , Kawasaki Shiro , Uno Toshihiko , Ohashi Yuichi
Published: March 2014

Purpose: To evaluate ocular surface temperature in assessing the efficacy of anti-allergic eye drops. Methods: Thirteen asymptomatic patients (24.7 ± 2.8 years) with proven seasonal allergic conjunctivitis due to cedar pollen were studied. A 0.025% levocabastine ophthalmic suspension was instilled in one eye (levocabastine eye) and artificial tears in the other eye (artificial tear eye) in a masked fashion 10 min prior to a conjunctival allergen challenge (CAC). Then, a drop of cedar pollen solution was dropped into the conjunctival sac to induce the allergic reaction. The surface temperature of the inferior bulbar conjunctiva was measured before and 30 min after the CAC with a newly developed non-contact ocular surface thermographer (OST). The degree of conjunctival injection and chemosis was also determined by slit-lamp biomicroscopy. The changes in the symptoms were evaluated by a questionnaire. Results: After the CAC, the temperature increased by 0.67 ± 0.10°C in the artificial tear eyes but by only 0.21 ± 0.06°C in the levocabastine eyes (p < 0.05). The score for conjunctival injection was 1.38 ± 0.24 and the chemosis score was 0.85 ± 0.25 for the artificial tear eyes and 0.62 ± 0.27 and 0.08 ± 0.08 in the levocabastine eyes (p < 0.01). The temperature increase was significantly correlated with the conjunctival injection scores (r = 0.63; p < 0.001). Conclusion: The significant correlation of the conjunctival surface temperature with the severity of the conjunctival allergic reaction indicates that the temperature measured by the OST can be used to objectively evaluate the efficacy of topical anti-allergic agents.
How Good Is the Neosquamous Epithelium?
Authors: Orlando Roy C.
Published: March 2014

Background/Aims: Endoscopic radiofrequency ablation of dysplastic Barrett's esophagus (BE) combined with proton pump inhibitor therapy is commonly utilized for preventing progression of dysplastic BE to esophageal adenocarcinoma. Fundamental to the success of this and all ablative approaches is the healing of the ablated areas of BE with a stratified squamous epithelium referred to as ‘neosquamous epithelium' (NSE). Although NSE appears ‘normal' endoscopically, the reemergence of BE over time in the previously ablated segments raises the question of the health and integrity of NSE. Methods: The health of NSE was recently investigated in endoscopic biopsies in vitro in a group of patients after ablation while on proton pump inhibitors. Biopsies of NSE were compared to upper squamous epithelium (USE) from the same patients morphologically (light microscopy) and with respect to barrier function by measuring electrical resistance and fluorescein flux in mini-Ussing chambers. Results: Compared to USE, NSE exhibited dilated intercellular spaces and inflammation and defective barrier function by low electrical resistance and high fluorescein flux. Moreover, NSE exhibited downregulation of claudin-4, a highly expressed protein in squamous tight junctions. Conclusion: NSE has defective barrier function in part due to downregulation of claudin-4. Since downregulation of claudin-4 increases paracellular permeability to cations, e.g. hydrogen ions, NSE is more vulnerable to attack and damage by acidic and weakly acidic refluxates - a phenomenon that may contribute in part to the reemergence of BE.
Non- and Semi-Invasive Methods of Monitoring Eosinophilic Esophagitis
Authors: Menard-Katcher Calies , Furuta Glenn T.
Published: March 2014

Background/Aims: Monitoring inflammation associated with eosinophilic esophagitis (EoE) relies on the identification of biomarkers that provide an objective measure of disease activity. To date, this metric has been the number of eosinophils in the squamous epithelial tissue. The search for alternative biomarkers as well as alternative methods to capture them has been the topic of much research. Methods: Based on clinical experience and a review of the literature, the aim of this chapter is to identify potential EoE biomarkers and methods to assess them. Results: With respect to the biomarkers, a number of candidates have arisen, including peripheral blood eosinophils, eosinophil granule proteins, Th2-related cytokines and exhaled nitric oxide. Methods to assess these biomarkers have included peripheral blood, luminal lavages and breath collections. Conclusions: Future research will identify the best clinical outcome measure for EoE. While mucosal eosinophilia currently serves as a well-defined metric of inflammation, newer research studies will continue to address whether this number correlates reliably with other patient-reported outcomes, endoscopic findings, molecular analyses or other yet to be defined biomarkers.
Sight-Threatening Ocular Manifestations of Acute Febrile Neutrophilic Dermatosis (Sweet's Syndrome)
Authors: Baartman Brandon , Kosari Payman , Warren Clinton C. , Ali Saba , Jorizzo Joseph L. , Sato Masaki , Kurup Shree K.
Published: March 2014

Sweet's syndrome is a primarily dermatologic disorder with many features of systemic inflammation. It is generally characterized by a neutrophilic dermatosis in the setting of fever and an elevated white blood cell count. Inflammation has been described to occur in many organ systems including the lung, bone, liver, spleen, brain and eye. Ocular inflammation is a well-known comorbidity that may occur in the setting of Sweet's syndrome, including conjunctivitis, episcleritis, scleritis, iritis and choroiditis, among other forms. In the current article, we have compiled a series of cases that describe three separate patients who demonstrated a rare form of ocular involvement in Sweet's syndrome, retinal vasculitis. The evidence from these three cases and other reports in recent ophthalmologic literature suggest overlapping of ocular manifestations of Sweet's syndrome and the closely related Behçet's disease. It is important to be aware of the sometimes challenging differential between these two disorders and their sight-threatening complications.
Dysphagia Risk Assessment in Acute Left-Hemispheric Middle Cerebral Artery Stroke
Authors: Somasundaram Sriramya , Henke Christian , Neumann-Haefelin Tobias , Isenmann Stefan , Hattingen Elke , Lorenz Matthias W. , Singer Oliver C.
Published: March 2014

Background and Purpose: Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. Methods: We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (<72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. Results: 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. Conclusions: In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control.
Impact of Antibiotic Prophylaxis on the Conjunctival Flora of Patients Receiving Intravitreal Antivascular Endothelial Growth Factor Injections
Authors: Picoto Passarinho Maria , Portelinha Joana R. , Pacheco Teresa J. , Rodrigues António E. , Marques Teresa P. , Vaz Fernanda F.
Published: March 2014

Purpose: To characterize the conjunctival flora of patients receiving antibiotics before intravitreal (IVT) antivascular endothelial growth factor injections. Methods: We studied 31 eyes of 30 patients with neovascular age-related macular degeneration scheduled to receive IVT antivascular endothelial growth factor injections. The patients were all given a preinjection of topical ofloxacin 3 days before the injections. Conjunctival cultures from the injection eye were collected before antibiotic prophylaxis (sample A) and on the injection day, both before (sample B) and after (sample C) povidone-iodine (PVI) application. Results: Culture positivity was significantly different between samples A (50%) and C (4.5%; p < 0.001) as well as samples B (30.4%) and C (4.5%; p = 0.015), but not between samples A and B. Positive cultures were mainly coagulase-negative staphylococci (CNS; 57% of sample A, 62.5% of sample B and 100% of sample C) susceptible to vancomycin (100%), moxifloxacin (90%), levofloxacin (70%) and ofloxacin (60%). Conclusion: In our study, most of the bacteria isolated were CNS. PVI application but not antibiotics reduced culture positivity.
Fluticasone Furoate Inhibits Cytokine Secretion from Nasal Epithelial Cells and Reduces Eosinophil Survival in an in vitro Model of Eosinophilic Inflammation
Authors: Mullol Joaquim , Pujols Laura , Alobid Isam , Pérez-Gonzalez Maria , Fuentes Mireya , de Borja Callejas Francisco , Valero Antonio , Picado Cesar , Roca-Ferrer Jordi
Published: March 2014

Background: Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic rhinitis (AR). However, the anti-inflammatory effects of FF in the nasal mucosa have yet to be investigated thoroughly. The aim of this study was to investigate the effect of FF on eosinophil survival and cytokine secretion from nasal mucosa epithelial cells. Methods: Epithelial cells obtained from nasal mucosa were stimulated with 10% fetal bovine serum (FBS) in the presence of FF (from 10-12 to 10-7M) for 6-24 h. Cytokine [granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-8] concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated for 4 days with epithelial cell secretions in the presence or absence of FF (from 10-12 to 10-7M) and survival was assessed by Trypan blue dye exclusion. Results are expressed as medians of the minimum effective concentration and IC values. Results: FBS stimulated the secretion of GM-CSF, IL-6 and IL-8. FF significantly inhibited GM-CSF (up to 10-10M, IC25 = 12.6 pM), IL-6 (up to 10-10M, IC25 = 65.8 pM) and IL-8 (up to 10-11M, IC25 = 8.6 pM) secretion induced by FBS (n = 8). Epithelial cell secretions induced eosinophil survival from day 1 to day 4 (n = 6). This effect was significantly inhibited by FF (up to 10-12M) at day 3 (IC50 = 3.22 nM) and day 4 (IC50 = 1.29 nM). Conclusions: The results obtained in this in vitro model suggest that FF may reduce upper airway eosinophilic inflammation through decreasing cytokine secretion from epithelial cells and reducing eosinophil survival.
Bioavailability and Allergoprotective Capacity of Milk-Associated Conjugated Linoleic Acid in a Murine Model of Allergic Airway Inflammation
Authors: Böcking Christian , Harb Hani , Ege Markus Johannes , Zehethofer Nicole , Fischer Kathleen , Krauß Julia , Holst Otto , Nüsing Rolf M. , Lindner Buko , von Mutius Erika , Renz Harald , Garn Holger , Pfefferle Petra Ina
Published: March 2014

Background: Cross-sectional epidemiological studies have demonstrated that farm milk from traditional farm settings possesses allergoprotective properties. Up to now, it has not been clarified which milk ingredient is responsible for protection against allergic diseases. As farm milk is rich in conjugated linoleic acids (CLA), it is hypothesized that this n-3 polyunsaturated fatty acid family contributes to the allergoprotective capacity of farm milk. We aim to prove this hypothesis in a murine model of allergic airway inflammation. Methods: To prove the bioavailability and allergoprotective capacity of milk-associated CLA in a standardized protocol, milk batches that differed significantly in terms of their CLA content were spray dried and incorporated into a basic diet by substituting the regular sunflower fat fraction. Initially, the milk CLA uptake from the diet was monitored via measurement of the CLA content in plasma and erythrocyte membranes obtained from supplemented mice. To determine whether a milk CLA-enriched diet possesses allergoprotective properties, female Balb/c mice were fed the milk CLA-enriched diet ahead of sensitization and a challenge with ovalbumin (OVA) and the parameters of airway inflammation and eisosanoid pattern were measured. Results: In animals, supplementation with a diet rich in milk CLA resulted in elevated CLA levels in plasma and erythrocyte membranes, indicating bioavailability of milk fatty acids. Though membrane-associated phospholipid patterns were affected by supplementation with milk CLA, this application neither reduced the hallmarks of allergic airway inflammation in sensitized and OVA-challenged mice nor modified the eiconsanoid pattern in the bronchoalveolar lavage fluid of these animals. Conclusion: Milk-associated CLA was not capable of preventing murine allergic airway inflammation in an animal model of OVA-induced allergic airway inflammation.
Short-Term Prognosis of Transient Ischemic Attack and Predictive Value of the ABCD2 Score in Hong Kong Chinese
Authors: Chiu Lai Hong Simon , Yau Wah Hon , Leung Ling Pong , Pang Peter , Tsui Chee Tat , Wan Kuang An , Au Thomas Tak-shun , Fong Wing Chi , Chung Shun Hang Joseph ,   On behalf of the Hong Kong TIA (HKTIA) project coinvestigators
Published: March 2014

Background: Literature on prognosis of transient ischemic attack (TIA) in Chinese is scarce. The short-term prognosis of TIA and the predictive value of the ABCD2 score in Hong Kong Chinese patients attending the emergency department (ED) were studied to provide reference for TIA patient management in our ED. Methods: A cohort of TIA patients admitted through the ED to 13 acute public hospitals in 2006 was recruited through the centralized electronic database by the Hong Kong Hospital Authority (HA). All inpatients were e-coded by the HA according to the International Classification of Diseases, Ninth Revision (ICD9). Electronic records and hard copies were studied up to 90 days after a TIA. The stroke risk of a separate TIA cohort diagnosed by the ED was compared. Results: In the 1,000 recruited patients, the stroke risk after a TIA at days 2, 7, 30, and 90 was 0.2, 1.4, 2.9, and 4.4%, respectively. Antiplatelet agents were prescribed in 89%, warfarin in 6.9%, statin in 28.6%, antihypertensives in 39.3%, and antidiabetics in 11.9% of patients after hospitalization. Before the index TIA, the prescribed medications were 27.6, 3.7, 11.3, 27.1, and 9.7%, respectively. The accuracy of the ABCD2 score in predicting stroke risk was 0.607 at 7 days, 0.607 at 30 days, and 0.574 at 90 days. At 30 days, the p for trend across ABCD2 score levels was 0.038 (OR for every score point = 1.36, p = 0.040). Diabetes mellitus, previous stroke and carotid bruit were associated with stroke within 90 days (p = 0.038, 0.045, 0.030, respectively). A total of 45.4% of CTs of the brain showed lacunar infarcts or small vessel disease. There was an increased stroke risk at 90 days in patients with old or new infarcts on CT or MRI. Patients with carotid stenosis ≥70% had an increased stroke risk within 30 (OR = 6.335, p = 0.013) and 90 days (OR = 3.623, p = 0.050). Stroke risks at days 2, 7, 30, and 90 in the 289 TIA patients diagnosed by the ED were 0.35, 2.4, 5.2, and 6.2%, respectively. Conclusion: The short-term stroke risk in Hong Kong Chinese TIA patients is low. The administered nonurgent treatment cannot solely explain the favorable outcome, the lower risk can be due to the different pathophysiological mechanisms of stroke between Caucasians and Chinese. The predictive value of the ABCD2 score is low in our population.
Vitronectin Regulation of Vascular Endothelial Growth Factor-Mediated Angiogenesis
Authors: Li Rong , Luo Mao , Ren Meiping , Chen Ni , Xia Jiyi , Deng Xin , Zeng Min , Yan Kai , Luo Tingting , Wu Jianbo
Published: March 2014

Background: Vascular endothelial growth factor (VEGF) plays a key role in regulating angiogenesis, and this process is largely dependent on the newly formed extracellular matrix (ECM). The levels of vitronectin (VN) are increased in patients with various cardiovascular diseases. A role for VN in regulating VEGF-induced angiogenesis has not been previously reported. We tested the hypothesis that VN regulates VEGFR-2 activation via effects on αvβ3, thus contributing to angiogenesis. Methods: We used a 3-dimensional angiogenesis assay, and examined the effects of VN on VEGF-mediated angiogenesis in aortic endothelial cells (ECs) isolated from wild-type and VN-deficient mice. Results: The addition of multimeric VN significantly enhanced VEGF-induced increases in EC migration and capillary formation. In vitro, Vn-/- ECs migrated significantly slower than wild-type ECs. The addition of VN to Vn-/- ECs increased EC migration and augmented the promigratory effect of VEGF in a manner that involved VEGFR-2 and Src signaling. Analysis of the mechanisms involved revealed that multimeric VN, but not monomeric VN, binds VEGF and enhances VEGF-induced VEGFR-2/Src activation in ECs. Conclusion: These results underscore the importance of VN in the regulation of angiogenesis induced by VEGF.
Complete Remission of Brain Metastases in Non-Small Cell Lung Cancer Patients Harboring an EGFR Mutation Treated with Tyrosine Kinase Inhibitor without Radiotherapy: A Report of 3 Cases
Authors: Jung Yun Hwa , Han Chi Wha , Jung Yun Duk , Cho Young Yun , Han Deok Jae
Published: March 2014

Brain parenchymal metastasis from a solid tumor is a serious clinical condition associated with a poor outcome because systemic chemotherapy is usually ineffective for treating brain metastases (BM) due to the blood-brain barrier. Therefore, radiotherapy such as whole brain radiotherapy (WBRT) and stereotactic radiosurgery have taken on a central role in the management of BM. However, WBRT can delay subsequent systemic treatment or cause neurologic complications such as a decline in cognitive function. Therefore, suspending WBRT is worth considering if there is an effective alternative. Although there have been no large prospective studies, many reports are available about the favorable effect of tyrosine kinase inhibitors (TKIs) for treating BM in patients with non-small cell lung cancer (NSCLC). Here, we report 3 NSCLC cases that showed a complete response in BM after TKI treatment without WBRT. Based on these remarkable response rates of BM to a TKI, the potential toxicity of WBRT can be avoided, particularly in patients with small metastatic nodules and an epidermal growth factor receptor activating mutation.
Representativeness of RELAX-AHF Clinical Trial Population in Acute Heart Failure
Authors: Wang Teresa S. , Hellkamp Anne S. , Patel Chetan B. , Ezekowitz Justin A. , Fonarow Gregg C. , Hernandez Adrian F.
Published: March 2014

Background—

The Relaxin for the Treatment of Acute Heart Failure (RELAX-AHF) trial enrolled 1161 patients admitted to the hospital for acute heart failure (AHF) to evaluate the therapeutic efficacy of serelaxin, a recombinant form of human relaxin-2. We characterized how representative RELAX-AHF clinical trial enrollees were to those patients with AHF found in international registries.

Methods and Results—

We examined 196 770 AHF admissions from the Acute Decompensated Heart Failure National Registry-United States and Acute Decompensated Heart Failure National Registry-International registries. Patients were considered RELAX-AHF-type if they met the following criteria: discharge diagnosis of heart failure, systolic blood pressure >125 mm Hg, dyspnea at rest or with mild exertion, intravenous diuretic use, glomerular filtration rate of 30 to 75 mL/min per 1.73 m
2
, hemoglobin >8 g/dL, and no use of intravenous inotropes or vasopressors. Baseline characteristics and treatments of RELAX-AHF-type and non–RELAX-AHF-type patients were compared. A Cox model was used to evaluate inpatient mortality. Among both Acute Decompensated Heart Failure National Registry-United States and Acute Decompensated Heart Failure National Registry-International registries, 20.7% (n=38 485) and 16.2% (n=1749) of patients met basic criteria for RELAX-AHF entry, respectively. These patients were more likely to be older, be women, have a previous history of hypertension, have preserved ejection fraction, and have better renal function. In-hospital mortality was lower in RELAX-AHF-type than in non–RELAX-AHF-type patients, even after multivariable adjustment (hazard ratio, 0.59; 95% confidence interval, 0.53–0.66;
P
<0.0001).

Conclusions—

Patients potentially eligible for RELAX-AHF represent ≈2 in 10 patients with AHF in the United States, Latin America, or Asia-Pacific. These patients differ significantly from other hospitalized patients based on clinical characteristics and outcomes.
Satisfaction With Emergent Transfer for Percutaneous Coronary Interventions on Patients With ST–Segment-Elevation Myocardial Infarction and Their Families
Authors: Henry Jason T. , Christiansen Ellen , Garberich Ross F. , Handran Chauncy B. , Larson David M. , Unger Barbara T. , Henry Timothy D.
Published: March 2014

Background—

Transfer for primary percutaneous coronary intervention (PCI) is superior to fibrinolysis if performed in a timely manner but frequently requires dislocation of patients and their families from their local community. Although patient satisfaction is increasingly viewed as an important quality indicator, there are no data on how emergent transfer for PCI affects patients with ST–segment-elevation myocardial infarction and their families.

Methods and Results—

The Minneapolis Heart Institute’s Level 1 Regional ST–Segment-Elevation Myocardial Infarction program is designed to facilitate emergent transfer for PCI in patients with ST–segment-elevation myocardial infarction from 31 rural and community hospitals. To determine the effect of emergent transfer, questionnaires were given to 152 patients and their families who survived to hospital discharge with a 65.8% response rate (mean age, 63.9 years; 29% women). Ninety-five percent of patients felt the reasons and process of transfer were well explained, and 97% felt transfer for care was necessary. Despite this, 15% of patients would have preferred to stay in their local hospital. The majority of the families felt the transfer process (88%) and family member’s condition (94%) were well explained. Although 99% felt it was necessary for their family member to be transferred for specialized care, 11% of families still would have preferred that their family members remain at the local community hospital.

Conclusions—

Our results suggest that ST–segment-elevation myocardial infarction patients and families can be informed, even in time-critical situations, about the transfer process for PCI and understand the need for specialized care. Still, a significant minority would prefer to stay at their local hospital, despite acknowledging transfer for PCI provided optimal care.
Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort
Authors: Olivot Jean Marc , Mlynash Michael , Inoue Manabu , Marks Michael P. , Wheeler Hayley M. , Kemp Stephanie , Straka Matus , Zaharchuk Gregory , Bammer Roland , Lansberg Maarten G. , Albers Gregory W.
Published: March 2014

Background and Purpose—

We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2).

Methods—

Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days.

Results—

Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (
P
<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (
P
<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3–14.3);
P
=0.014.

Conclusions—

HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.
Early-Onset Seizures Are Correlated With Late-Onset Seizures in Children With Arterial Ischemic Stroke
Authors: Hsu Chen-Jui , Weng Wen-Chin , Peng Steven Shinn-Feng , Lee Wang-Tso
Published: March 2014

Background and Purpose—

Early-onset seizures are common in children with arterial ischemic stroke, but the clinical features and effects on the outcome of early-onset seizures have been less studied in children.

Methods—

Children aged 1 month to 18 years presenting with first-time and image-confirmed arterial ischemic stroke were identified for analysis.

Results—

A total of 78 survivors of arterial ischemic stroke were enrolled. Twenty (25.6%) had early-onset seizures, and 90% were initial presentation. Younger children (mean, 3.4±3.9 versus 9.0±6.2 years;
P
<0.001) and cortical involvement (5% versus 63.8%;
P
=0.01) are more likely to have early-onset seizures. Thirteen of 20 survivors with early-onset seizures had late-onset seizures after the acute stage, and 12 of them were diagnosed as poststroke epilepsy.

Conclusions—

Early-onset seizures occurred in 25.6% of children with arterial ischemic stroke. Younger age and cortical involvement were risk factors for early-onset seizures. Sixty-five percent of children with early-onset seizures had late-onset seizures after the acute stage.
New data on the recently described Xiphion heracleanum (Iridaceae), endemic to Morocco
Authors: Crespo Manuel B. , Alonso María Angeles , Martínez-Azorín Mario , Vicente Alicia , Villar José Luis , Chambouleyron Mathieu
Published: March 2014

Xiphion heracleanum was recently described from the Tingitane Peninsula (northern Morocco), on the basis of herbarium material collected mostly in the 19th century. After field work in the Rif area, a new population with three independent subpopulations of X. heracleanum has been discovered in Djebel Bouhachem, over 60 km southeast from Tangiers, the type locality. About 100 reproductive individuals are growing there, on schistose soils in rocky places. New data on morphology, ecology, and distribution of this taxon are reported on the basis of re-evaluation of characters from both living specimens and herbarium material, and morphological affinities and differences with close relatives in the genus are discussed. In particular, relationships with the North African endemic X. junceum are newly revised, a morphologically very close plant which is lectotypified here and as which it has repeatedly been misidentified. Furthermore, inclusion of this species in the list of rare plants of Morocco is proposed as RR, and a key for identification of the known species of Xiphion is presented.
Lymphatic Obstruction
Authors: Mostafa Hany S. , Fawzy Tamer O. , Jabri Waleed R. , Ayad Essam
Published: March 2014

Objectives:

Antrochoanal polyps (ACPs) originate from the inner wall of the maxillary sinus and either pass through the natural sinus ostia or cause pressure-induced destruction of the medial sinus wall. Eventually, they extend into the choanae and nasopharynx. Most authors who have studied the microstructure of ACPs, including the component stromal cells and surface epithelium, have not examined the transitional area between the sinus mucosa and the pedicle of the polyp. No explanation has been given for the absence of a cystic intrasinus portion of the polyp, in many cases refuting the therapy (most accepted) that polyps are caused by a mucous gland with a blocked acinus. We noted during endoscopic removal of the ACPs that the antral part of the polyp was cystic in only 5% of patients, and polypoid in 95%. The cystic intrasinus portion of the polyp is a cornerstone of the pathophysiology of ACPs, whether caused by inflammation, cicatrization, or allergy. This finding prompted us to examine the transitional area between the sinus mucosa and the pedicle of the polyp to verify the possibility that lymphatic obstruction—whether primary (areas of higher tissue pressure) or secondary (cicatrization or inflammation)—could be an etiologic factor in the formation of ACPs.

Methods:

The study material consisted of 25 ACPs and 25 chronic maxillary sinusitis mucosal biopsy specimens (control group). The detection of lymphatic vessels was based on the identification of lymph vessel endothelial hyaluronic acid receptor 1 (LYVE-1) in the endothelial cells of the lymphatic capillaries. This was the first lymph-specific hyaluronic acid receptor to be characterized, and is a uniquely powerful marker for lymph vessels, differentiating them from (blood) capillaries.

Results:

The density of the lymphatic vessels was marked in 22 of the 25 ACP specimens, ie, 88% of the ACP cases, compared with 16% of the control group.

Conclusions:

This study resulted in two main findings. The first was the absence of intramaxillary cysts in the ACPs in 23 cases (92%). The second was the markedly high density of lymphatic vessels in the transitional area between the sinus mucosa and the pedicle of the ACPs, in comparison with the density in the control group. These two findings refute the “blocked acinus theory” and indicate that lymphatic obstruction, whether primary or secondary to chronic sinus infection, might play a leading role in the formation and further growth of ACPs.