bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine/anti‐cytokine therapy – novel treatments for asthma?
Authors: Hansbro Philip M , Kaiko Gerard E , Foster Paul S 
Published: January 2011

Asthma is a chronic inflammatory disease of the airways and there are no preventions or cures. Inflammatory cells through the secretion of cytokines and pro‐inflammatory molecules are thought to play a critical role in pathogenesis. Type 2 CD4+ lymphocytes (Th2 cells) and their cytokines predominate in mild to moderate allergic asthma, whereas severe steroid‐resistant asthma has more of a mixed Th2/Th1 phenotype with a Th17 component. Other immune cells, particularly neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease‐associated cytokines in asthma. Increased levels of these immune cells and cytokines have been identified in clinical samples and their potential role in disease demonstrated in studies using mouse models of asthma. Clinical trials with inhibitors of cytokines such as interleukin (IL)‐4, ‐5 and tumour necrosis factor‐α have had success in some studies but not others. This may reflect the design of the clinical trials, including treatments regimes and the patient population included in these studies. IL‐13, ‐9 and granulocyte‐macrophage colony‐stimulating factor are currently being evaluated in clinical trials or preclinically and the outcome of these studies is eagerly awaited. Roles for IL‐25, ‐33, thymic stromal lymphopoietin, interferon‐γ, IL‐17 and ‐27 in the regulation of asthma are just emerging, identifying new ways to treat inflammation. Careful interpretation of results from mouse studies will inform the development and application of therapeutic approaches for asthma. The most effective approaches may be combination therapies that suppress multiple cytokines and a range of redundant and disconnected pathways that separately contribute to asthma pathogenesis. Astute application of these approaches may eventually lead to the development of effective asthma therapeutics. Here we review the current state of knowledge in the field.LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐1
Genetics of complex respiratory diseases: implications for pathophysiology and pharmacology studies
Authors: Obeidat Ma'en , Hall Ian P. 
Published: January 2011

There has been a huge influx of data on the genetics and genomics of respiratory diseases in the last few years. Powered by large sample sizes from collaborations worldwide, recent genome‐wide association studies have convincingly implicated variants in different regions in the genome for association with complex respiratory traits. These new associations have the potential to offer invaluable insight into the pathophysiology of the normal and diseased respiratory system. The functional mechanisms underlying effects of both identified and novel variants will be the focus of research over the next few years. The identification of these mechanisms will not only increase our understanding of disease but may allow the development of new therapies to alleviate respiratory conditions. The implications of these approaches for studies of asthma and Chronic Obstructive Pulmonary Disease are covered in this review.LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐1
Vicenza International Courses on hemodialysis: Educational events where science meets clinical practice
Authors: RONCO Claudio 
Published: January 2011

AbstractInternational Vicenza Courses represent important educational events held yearly in the city of Palladio. Claudio Ronco organizes since 1982 international courses on peritoneal dialysis, hemodialysis and critical care nephrology. The faculty is outstanding and the content very informative and useful for beginners and for experts in the various fields. Every year the entire course is recorded in a DVD and the proceedings are available at the beginning of the course. Information can be obtained at http://www.vicenzanephrocourses.com.
Combination of Testosterone and Vardenafil Increases Female Sexual Functioning in Sub-Primed Rats
Authors: Snoeren Eelke M.S. , Bovens Astrid , Refsgaard Louise K. , Westphal Koen G.C. , Waldinger Marcel D. , Olivier Berend , Oosting Ronald S. 
Published: January 2011

ABSTRACT

Introduction
Hypoactive sexual desire disorder (HSDD) is a common problem in women and may have a negative impact on quality of life. A recent clinical study shows an increase in sexual drive of HSDD women after cotreatment of testosterone and vardenafil (phosphodiesterase type 5 inhibitor).

Aim
In this study, we investigated the effect of testosterone and vardenafil on sexual activity in female rats.

Main Outcome Measures
Proceptive (darts and hops), receptive (lordosis), and paced-mating (percentages after exits and contact-return latencies) behaviors were quantified.

Methods
Ovariectomized female rats, sub-primed with only estradiol and fully primed with estradiol and progesterone, were tested in a paced-mating sex test and sexual behaviors were quantified. The sub-primed rats are thought to model HSDD. The effect of testosterone (100 and 300 µg, subcutaneous [SC]) and vardenafil (10 mg/kg, per os [PO]) alone and testosterone (300 µg, SC) in combination with vardenafil (3 and 10 mg/kg, PO) were tested. We also studied the effects of testosterone (300 µg, SC) + intracerebroventricular (ICV) injections of vardenafil (25 and 50 µg) on sexual activity.

Results
No effect of testosterone and vardenafil alone was found, but cotreatment of testosterone and vardenafil (PO) caused a significant increase in proceptive and receptive behavior in the sub-primed female rats. Testosterone and vardenafil did not affect fully primed females. ICV administration of vardenafil combined with systemic testosterone, on the other hand, had no effect on sexual activity in both sub-primed and fully primed female rats.

Conclusions
We conclude that cotreatment of subcutaneous testosterone and oral vardenafil increase sexual activity in sub-primed female rats. Our data supports the human finding that combination treatment of testosterone and vardenafil could be used as a new treatment for women with HSDD.
Small cell lung cancer presenting with paraneoplastic limbic encephalitis
Authors: BOWYER Samantha , WEBB Suzanne , MILLWARD Michael , JASAS Kevin , BLACKER David , NOWAK Anna 
Published: January 2011

AbstractWe report two cases of the rare neurological paraneoplastic syndrome, limbic encephalitis, as the initial presentation of small cell lung cancer. The first case responded to treatment of the underlying malignancy, while the second required more acute treatment in the intensive care setting. In this case, initial treatment was with immunosuppression to achieve a degree of stability before the underlying malignancy could be treated. Both cases had significant improvement in neurological function. These cases highlight the importance of directed investigation to try and identify an underlying malignancy in patients in whom a diagnosis of limbic encephalitis is made, and the difficulty in managing such patients.
Corneal hysteresis in mucopolysaccharidosis I and VI
Authors: Fahnehjelm Kristina Teär , Chen Enping , Winiarski Jacek 
Published: January 2011

Abstract.Purpose:  High intraocular pressure (IOP) and glaucoma are often suspected in patients with mucopolysaccharidosis (MPS). To determine corneal hysteresis (CH) and IOP in children with mucopolysaccharidosis I‐Hurler (MPS I‐H) and MPS VI.Methods:  Clinical measurements with ocular response analyzer (ORA).Results:  In seven patients, five with MPS I‐H treated with stem cell transplantation (SCT), and two with MPS VI, one treated with SCT and the other with enzyme therapy, the IOP was examined with ORA. Ocular response analyzer measurements were made at a median age of 8.7 years in the patients with MPS I‐H and at a median age of 9.3 years in the patients with MPS VI. Earlier measurements had raised suspicion of high IOP in one patient. The ORA showed an increased CH and a falsely high IOP values in all 14 eyes. The recalculated IOPs were normal in all 14 eyes. Mild to severe corneal opacities were present in all 14 eyes. Optic disc areas, borders and cupping were clinically normal in the 12 of 14 eyes that were possible to examine. Severe corneal opacities hampered optic disc evaluation in the older patient with MPS VI. Three eyes in two patients had normal thickness of the retinal nerve fibre layer measured with scanning laser polarimetry with corneal compensation (GDx VCC). No patient was diagnosed or treated for glaucoma.Conclusion:  The IOPs are often falsely high because of an increased resistance of the cornea and correlate to the extent of corneal clouding. In this small, cross‐sectional study, it appears that corneal resistance is directly correlated with corneal clouding, although a longitudinal study that evaluates resistance as the cornea clears with treatment would provide more direct evidence that corneal deposits are directly related to resistance. A correct measured IOP can avoid unnecessary medical or surgical hypotensive treatment.
Effect and mechanism of senkyunolide I as an anti-migraine compound from Ligusticum chuanxiong
Authors: Wang Yi-Han , Liang Shuang , Xu De-Sheng , Lin Xiao , He Chun-Yong , Feng Yi , Hong Yan-Long 
Published: January 2011

Abstract

Objective
To evaluate the analgesic and anti-migraine activities of senkyunolide I from Ligusticum chuanxiong.

Methods
Mice were orally administered various doses of senkyunolide I, and their pain levels were assessed in a hot-plate test and by application of acetic acid. The levels of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) in plasma and brain were assessed, and the monoamine turnover rates (5-HT/5-HTP, 5-HIAA/5-HT and NE/DA) were also calculated.

Results
Mice given senkyunolide I at 16 and 32 mg/kg had significantly elevated pain thresholds in the hot-plate test, and a dose of 32 mg/kg also reduced the number of abdominal writhing responses caused by acetic acid. Significant improvements were observed in the neurotransmitter levels of the drug-treated rats compared with the saline-administered controls. Compared to the rats with nitroglycerin-induced migraines, the levels of nitric oxide in the plasma and whole brain of rats given senkyunolide I were lower.

Conclusions
The present study suggests that senkyunolide I may be an active component of L. chuanxiong, traditionally used to treat migraine. The mechanism of pain relief in migraine model rats may be through adjusting the levels of monoamine neurotransmitters and their turnover rates, as well as decreasing nitric oxide levels in the blood and brain. Therefore, senkyunolide I may be developed as a potential treatment for migraine pain.
Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer
Authors: Gonzalez-Angulo Ana M. , Timms Kirsten M. , Liu Shuying , Chen Huiqin , Litton Jennifer K. , Potter Jennifer , Lanchbury Jerry S. , Stemke-Hale Katherine , Hennessy Bryan T. , Arun Banu K. , Hortobagyi Gabriel N. , Do Kim-Anh , Mills Gordon B. , Meric-Bernstam Funda 
Published: January 2011

Abstract
Purpose: To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation.
Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chi-square. Survival was estimated by Kaplan–Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome.
Results: Median age was 51 years (27–83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7–214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 73.3% for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95% CI: 0.045–0.79, P = 0.016) compared with WT.
Conclusions: In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse. Clin Cancer Res; 17(5); 1082–9. ©2011 AACR.
The CXCL16 A181V Mutation Selectively Inhibits Monocyte Adhesion to CXCR6 but Is Not Associated With Human Coronary Heart Disease
Authors: Petit Sarah J. , Wise Emma L. , Chambers John C. , Sehmi Jobanpreet , Chayen Naomi E. , Kooner Jaspal S. , Pease James E. 
Published: January 2011

Objective—

The chemokine CXCL16 serves as a scavenger receptor for oxidized low-density lipoprotein and as an adhesion molecule and chemoattractant for cells expressing the receptor CXCR6. A commonly occurring
CXCL16
allele has been described containing 2 nonsynonymous single-nucleotide polymorphisms in complete linkage disequilibrium, although the effects on CXCL16 function are unknown. Here, we examined the effect of the single-nucleotide polymorphisms on CXCL16 function and assessed the association of the mutant allele with coronary heart disease (CHD).

Methods and Results—

Both wild-type and mutant T123V181-CXCL16 were readily expressed in vitro and were similarly functional in assays of oxidized low-density lipoprotein scavenging and chemotaxis. However, unlike wild-type CXCL16, T123V181-CXCL16 was unable to promote adhesion of CXCR6
+
cells. Findings were confirmed ex vivo, with monocytes from donors homozygous for the
T123V181
allele unable to facilitate adhesion of CXCR6 transfectants. In the London Life Sciences Prospective Population cohort (n=2797), we found that the
T123V181
allele was not associated with protection or susceptibility to CHD (adjusted odds ratio, 1.01; 95% CI, 0.95 to 1.10;
P
=0.74).

Conclusion—
CXCL16-mediated cell adhesion plays at best a modest role in CHD, and the scavenging and chemotactic properties of the chemokine are more likely to be more important in disease pathogenesis.
High Shear Stress and Flow Velocity in Partially Occluded Aneurysms Prone to Recanalization
Authors: Luo Bin , Yang Xinjian , Wang Shengzhang , Li Haiyun , Chen Jialiang , Yu Hongyu , Zhang Ying , Zhang Yisen , Mu Shiqing , Liu Zhicheng , Ding Guanghong 
Published: January 2011

Background and Purpose—
Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. However, the hemodynamic features in the residual neck of the partially embolized aneurysms and their influences on recanalization are rarely reported. In this study, we characterized the hemodynamics of partially occluded aneurysms, which were proven to undergo recanalization during follow-up using computational fluid dynamic analysis.

Methods—
From May 2007 to June 2009, we identified 11 partial aneurysms during follow-up, including 5 recanalized cases and 6 stable cases with 3-dimensional digital subtraction angiography. We retrospectively characterized the hemodynamic features around the residual aneurismal pouch using the available postprocedural digital subtraction angiography image data. The occluded part of the aneurysm was regarded as completely separated from the circulation.

Results—
The overall blood flow patterns before embolization were almost the same in the recanalized and stable groups. After occlusion, the flow pattern changes, wall shear stress (WSS), and velocity at the remnant neck demonstrated different changes between the 2 groups. Specifically, in the recanalized group, high WSS regions were found near the neck in all 5 cases, with 4 of them being even higher than those before occlusion. Interestingly, in all cases, the high WSS area of the remnant neck coincided with the location where the aneurysm recanalization occurred. In the stable group, 5 out of 6 cases demonstrated lower WSS and velocity at the remnant neck after occlusion.

Conclusions—
High WSS and blood flow velocity were consistently observed near the remnant neck of partially embolized aneurysms prone to future recanalization, suggesting that hemodynamic factors may have an important role in aneurismal recurrence after endovascular treatment. The difference in flow pattern could be caused by the incomplete occlusion of the aneurysms.
Hypertensive Disorders in Pregnancy and Preterm Delivery and Subsequent Stroke in Asian Women
Authors: Wang I-Kuan , Chang Shih-Ni , Liao Chien-Chang , Liang Chih-Chia , Chang Chiz-Tzung , Lin Hsin-Hung , Liu Jiung-Hsiun , Liu Yao-Lung , Chuang Feng-Rong , Hsu Chung-Y. , Huang Chiu-Ching , Sung Fung-Chang 
Published: January 2011

Background and Purpose—
Few studies exist concerning the risk of stroke associated with hypertensive disorders in pregnancy (HDP) in Asian women. This study investigates whether preterm delivery further complicates this risk in women with HDP in Taiwan.

Methods—
Based on universal insurance claims data, 1092 pregnant women with newly diagnosed HDP from 2000 to 2004 and aged 15 to 40 years were identified as the HDP cohort. Then, 4715 randomly selected persons without HDP frequency matched with the index year were designated as the non-HDP controls. Both cohorts were followed-up until the end of 2008 to measure the incidence of stroke.

Results—

The HDP cohort had a higher incidence of stroke than the non-HDP cohort (30.1 vs 12.8 per 10 000 person-years), with an overall adjusted hazard ratio of 2.04 (95% CI, 1.18- 3.51) for stroke. Preterm delivery increased the risk of stroke to 3.22-fold (95% CI, 1.48–6.99;
P
for trend=0.002). The age-specific V-shape risk association showed that the highest risk of stroke was noted among subjects 15 to 18 years old in the HDP group (hazard ratio, 13.4; 95% CI, 1.54–116.7) and followed by women aged 35 years and older (hazard ratio, 5.56; 95% CI, 1.47–21.0).

Conclusions—
Pregnant women with HDP have an increased risk of subsequent stroke. Preterm delivery and older ages increase the risk of subsequent stroke. Adolescents with HDP also have an elevated risk of stroke. Early identification of women with HDP is needed for prevention.
A Syntacto-Cognitive Study of the Diachrony, Synchrony, Etymology and Gloss of the New Persian Formant am/an
Authors: Borbor Dariush 
Published: January 2011

AbstractThis paper presents a novel analysis of the Persian formant am-/an- in a broad context in order to clarify its diachrony, synchrony, etymology, and gloss. The formant is classified into two types: those derived from Old Iranian ham-/han- “together,” and those belonging to the cognitive process. These formants always convey four metaphoric cognitive percepts: collection/collocation, multiplicity, pluralism and infiltration. These percepts are manifested in three forms: receptacle; cluster, multiplicity, doubling; and, to a lesser degree, permeation. The study also explores the presence of some cross-language regularities in neighboring languages with the same cognitive concept of am-/an-, which conforms to the categories and classifications proposed by this paper.
Is Radiographic Measurement of Bony Landmarks Reliable for Lateral Meniscal Sizing?
Authors: Yoon Jung-Ro , Kim Taik-Seon , Lim Hong-Chul , Lim Hyung-Tae , Yang Jae-Hyuk 
Published: January 2011

Background: The accuracy of meniscal measurement methods is still in debate. Hypothesis: The authors’ protocol for radiologic measurements will provide reproducible bony landmarks, and this measurement method of the lateral tibial plateau will correlate with the actual anatomic value. Study Design: Controlled laboratory study. Methods: Twenty-five samples of fresh lateral meniscus with attached proximal tibia were obtained during total knee arthroplasty. Each sample was obtained without damage to the meniscus and bony attachment sites. The inclusion criterion was mild to moderate osteoarthritis in patients with mechanical axis deviation of less than 15°. Knees with lateral compartment osteoarthritic change or injured or degenerated menisci were excluded. For the lateral tibial plateau length measurements, the radiographic beam was angled 10° caudally at neutral rotation, which allowed differentiation of the lateral plateau cortical margins from the medial plateau. The transition points were identified and used for length measurement. The values of length were then compared with the conventional Pollard method and the anatomic values. The width measurement was done according to Pollard’s protocol. For each knee, the percentage deviation from the anatomic dimension was recorded. Intraobserver error and interobserver error were calculated. Results: The deviation of the authors’ radiographic length measurements from anatomic dimensions was 1.4 ± 1.1 mm. The deviation of Pollard’s radiographic length measurements was 4.1 ± 2.0 mm. With respect to accuracy—which represents the frequency of measurements that fall within 10% of measurements—the accuracy of authors’ length was 98%, whereas for Pollard’s method it was 40%. There was a good correlation between anatomic meniscal dimensions and each radiologic plateau dimensions for lateral meniscal width ( R2 = .790) and the authors’ lateral meniscal length ( R2 = .823) and fair correlation for Pollard’s lateral meniscal length ( R2 = .660). The reliability of each radiologic measurement showed good reliability (intraclass correlation coefficients, .823 to .973). The authors tried to determine the best-fit equation for predicting meniscal size from Pollard’s method of bone size, as follows: anatomic length = 0.52 × plateau length (according to Pollard’s method) + 5.2, not as Pollard suggested (0.7 × Pollard’s plateau length). Based on this equation—namely, the modified Pollard method—the percentage difference decreased, and the accuracy increased to 92%. Conclusion: Lateral meniscal length dimension can be accurately predicted from the authors’ radiographic tibial plateau measurements. Clinical Relevance: This study may provide valuable information in preoperative sizing of lateral meniscus in meniscal allograft transplantation.