bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Management of Adult Patients with a History of Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema: Update
Authors: Asero Riccardo
Published: May 2010

In the large majority of previous studies, patients with a history of acute urticaria induced by nonsteroidal anti-inflammatory drugs (NSAIDs) seeking safe alternative drugs have undergone tolerance tests uniquely with compounds exerting little or no inhibitory effect on the cyclooxygenase 1 enzyme. In light of recently published studies, however, this approach seems inadequate and should be changed. The present article critically reviews the clinical management of patients presenting with a history of urticaria induced by a single NSAID or multiple NSAIDs and suggests a simple, updated diagnostic algorithm that may assist clinicians in correctly classifying their patients.
Role of Genetic Polymorphisms in Therapeutic Response to Anti-Asthma Therapy
Authors: Oppenheimer John
Published: May 2010

Over the past several decades, significant advances have been seen in the diagnosis and treatment of asthma. Recent research has focused on potential phenotypic and genotypic predictors of response to therapy. In this review, we will examine each of the three major therapeutic classes of asthma therapy, focusing on a potential genetic clue to medication response.
Amoxicillin-Induced Eosinophilic Pneumonia with Granulomatous Reaction: Discrepancy between Drug-Induced Lymphocyte Stimulation Test Findings and the Provocation Drug Test
Authors: Matsuno Osamu , Takenaka Ryuichi , Ando Masaru , Miyazaki Eishi , Kumamoto Tosihide
Published: May 2010

A 59-year-old man was admitted to the hospital with pulmonary infiltration, fever, erythema, and eosinophilia. Two weeks before admission, he received amoxicillin, acetaminophen, and shoseiryu-to (a Japanese herbal medicine) for a common cold. Bronchoalveolar lavage was performed, and an increased number of eosinophils was recovered. Transbronchial biopsy specimens showed granuloma and interstitial thickening with eosinophils and lymphocytes. Drug-induced eosinophilic pneumonia was suspected, so all drugs were discontinued. The symptoms and infiltration shadow disappeared. A drug-induced lymphocyte stimulation test (DLST) was positive for acetaminophen but not for amoxicillin. In contrast to the DLST, a provocation test revealed that amoxicillin induced the drug allergy. A very striking observation was the coexistence of pulmonary eosinophilia and granulomatous lung infiltrations. In addition, there was a discrepancy between the DLST and provocation test findings. To our knowledge, there is no previous report of drug-induced eosinophilic pneumonia with a granulomatous reaction.
Primary Prevention of Allergic Diseases: Current Concepts and Mechanisms
Authors: Gerhold Kerstin , Darcan Yasemin , Hamelmann Eckard
Published: May 2010

Atopic diseases, the new "epidemic of the twenty-first century" and a central health problem of industrial nations, call for the development of innovative primary prevention strategies. The present review provides an overview of current experimental and immunomodulatory procedures and their underlying mechanisms.
Bronchodilator Response in Patients with Persistent Allergic Asthma Could Not Predict Airway Hyperresponsiveness
Authors: Petanjek Bojana B. , Grle Sanja P. , Pelicarić Dubravka , Vranković Dubravka
Published: May 2010

Anticholinergics, or specific antimuscarinic agents, by inhibition of muscarinic receptors cause bronchodilatation, which might correlate with activation of these receptors by the muscarinic agonist methacholine. The aim of this study was to determine whether a positive bronchodilator response to the anticholinergic ipratropium bromide could predict airway hyperresponsiveness in patients with persistent allergic asthma. The study comprised 40 patients with mild and moderate persistent allergic asthma. Diagnosis was established by clinical and functional follow-up (skin-prick test, spirometry, bronchodilator tests with salbutamol and ipratropium bromide, and methacholine challenge testing). The bronchodilator response was positive to both bronchodilator drugs in all patients. After salbutamol inhalation, forced expiratory volume in 1 second (FEV1) increased by 18.39 ± 6.18%,p< .01, whereas after ipratropium bromide, FEV1increased by 19.14 ± 6.74%,p< .01. The mean value of FEV1decreased by 25.75 ± 5.16%,p< .01 after methacholine (PC20FEV1[provocative concentration of methacholine that results in a 20% fall in FEV1] from 0.026 to 1.914 mg/mL). Using linear regression, between methacholine challenge testing and bronchodilator response to salbutamol, a positive, weak, and stastistically significant correlation for FEV1was found (p< .05). Correlations between methacholine challenge testing and the bronchodilator response to ipratropium bromide were positive and weak but not statistically significant. The positive bronchodilator response to ipratropium bromide could not predict airway hyperresponsiveness.
The zebra finch neuropeptidome: prediction, detection and expression
Authors: Xie Fang , London Sarah E , Southey Bruce R , Annangudi Suresh P , Amare Andinet , Rodriguez-Zas Sandra L , Clayton David F , Sweedler Jonathan V
Published: May 2010

Background

Among songbirds, the zebra finch (Taeniopygia guttata) is an excellent model system for investigating the neural mechanisms underlying complex behaviours such as vocal communication, learning and social interactions. Neuropeptides and peptide hormones are cell-to-cell signalling molecules known to mediate similar behaviours in other animals. However, in the zebra finch, this information is limited. With the newly-released zebra finch genome as a foundation, we combined bioinformatics, mass-spectrometry (MS)-enabled peptidomics and molecular techniques to identify the complete suite of neuropeptide prohormones and final peptide products and their distributions.

Results

Complementary bioinformatic resources were integrated to survey the zebra finch genome, identifying 70 putative prohormones. Ninety peptides derived from 24 predicted prohormones were characterized using several MS platforms; tandem MS confirmed a majority of the sequences. Most of the peptides described here were not known in the zebra finch or other avian species, although homologous prohormones exist in the chicken genome. Among the zebra finch peptides discovered were several unique vasoactive intestinal and adenylate cyclase activating polypeptide 1 peptides created by cleavage at sites previously unreported in mammalian prohormones. MS-based profiling of brain areas required for singing detected 13 peptides within one brain nucleus, HVC;in situhybridization detected 13 of the 15 prohormone genes examined within at least one major song control nucleus. Expression mapping also identified prohormone messenger RNAs in areas associated with spatial learning and social behaviours. Based on the whole-genome analysis, 40 prohormone probes were found on a commonly used zebra finch brain microarray. Analysis of these newly annotated transcripts revealed that six prohormone probes showed altered expression after birds heard song playbacks in a paradigm of song recognition learning; we partially verify this result experimentally.

Conclusions

The zebra finch peptidome and prohormone complement is now characterized. Based on previous microarray results on zebra finch vocal learning and synaptic plasticity, a number of these prohormones show significant changes during learning. Interestingly, most mammalian prohormones have counterparts in the zebra finch, demonstrating that this songbird uses similar biochemical pathways for neurotransmission and hormonal regulation. These findings enhance investigation into neuropeptide-mediated mechanisms of brain function, learning and behaviour in this model.
Mathematical framework for human SLE Nephritis: disease dynamics and urine biomarkers
Authors: Budu-Grajdeanu Paula , Schugart Richard C , Friedman Avner , Birmingham Daniel J , Rovin Brad H
Published: May 2010

Background

Although the prognosis for Lupus Nephritis (LN) has dramatically improved with aggressive immunosuppressive therapies, these drugs carry significant side effects. To improve the effectiveness of these drugs, biomarkers of renal flare cycle could be used to detect the onset, severity, and responsiveness of kidney relapses, and to modify therapy accordingly. However, LN is a complex disease and individual biomarkers have so far not been sufficient to accurately describe disease activity. It has been postulated that biomarkers would be more informative if integrated into a pathogenic-based model of LN.

Results

This work is a first attempt to integrate human LN biomarkers data into a model of kidney inflammation. Our approach is based on a system of differential equations that capture, in a simplified way, the complexity of interactions underlying disease activity. Using this model, we have been able to fit clinical urine biomarkers data from individual patients and estimate patient-specific parameters to reproduce disease dynamics, and to better understand disease mechanisms. Furthermore, our simulations suggest that the model can be used to evaluate therapeutic strategies for individual patients, or a group of patients that share similar data patterns.

Conclusions

We show that effective combination of clinical data and physiologically based mathematical modeling may provide a basis for more comprehensive modeling and improved clinical care for LN patients.
Analysis of Prototype Foamy Virus particle-host cell interaction with autofluorescent retroviral particles
Authors: Stirnnagel Kristin , Lüftenegger Daniel , Stange Annett , Swiersy Anka , Müllers Erik , Reh Juliane , Stanke Nicole , Große Arend , Chiantia Salvatore , Keller Heiko , Schwille Petra , Hanenberg Helmut , Zentgraf Hanswalter , Lindemann Dirk
Published: May 2010

Background

The foamy virus (FV) replication cycle displays several unique features, which set them apart from orthoretroviruses. First, like other B/D type orthoretroviruses, FV capsids preassemble at the centrosome, but more similar to hepadnaviruses, FV budding is strictly dependent on cognate viral glycoprotein coexpression. Second, the unusually broad host range of FV is thought to be due to use of a very common entry receptor present on host cell plasma membranes, because all cell lines tested in vitro so far are permissive.

Results

In order to take advantage of modern fluorescent microscopy techniques to study FV replication, we have created FV Gag proteins bearing a variety of protein tags and evaluated these for their ability to support various steps of FV replication. Addition of even small N-terminal HA-tags to FV Gag severely impaired FV particle release. For example, release was completely abrogated by an N-terminal autofluorescent protein (AFP) fusion, despite apparently normal intracellular capsid assembly. In contrast, C-terminal Gag-tags had only minor effects on particle assembly, egress and particle morphogenesis. The infectivity of C-terminal capsid-tagged FV vector particles was reduced up to 100-fold in comparison to wild type; however, infectivity was rescued by coexpression of wild type Gag and assembly of mixed particles. Specific dose-dependent binding of fluorescent FV particles to target cells was demonstrated in an Env-dependent manner, but not binding to target cell-extracted- or synthetic- lipids. Screening of target cells of various origins resulted in the identification of two cell lines, a human erythroid precursor- and a zebrafish- cell line, resistant to FV Env-mediated FV- and HIV-vector transduction.

Conclusions

We have established functional, autofluorescent foamy viral particles as a valuable new tool to study FV - host cell interactions using modern fluorescent imaging techniques. Furthermore, we succeeded for the first time in identifying two cell lines resistant to Prototype Foamy Virus Env-mediated gene transfer. Interestingly, both cell lines still displayed FV Env-dependent attachment of fluorescent retroviral particles, implying a post-binding block potentially due to lack of putative FV entry cofactors. These cell lines might ultimately lead to the identification of the currently unknown ubiquitous cellular entry receptor(s) of FVs.
Merotelic attachments and non-homologous end joining are the basis of chromosomal instability
Authors: Guerrero Astrid Alonso , Martínez-A Carlos , van Wely Karel HM
Published: May 2010

Although the large majority of solid tumors show a combination of mitotic spindle defects and chromosomal instability, little is known about the mechanisms that govern the initial steps in tumorigenesis. The recent report of spindle-induced DNA damage provides evidence for a single mechanism responsible for the most prominent genetic defects in chromosomal instability. Spindle-induced DNA damage is brought about by uncorrected merotelic attachments, which cause kinetochore distortion, chromosome breakage at the centromere, and possible activation of DNA damage repair pathways. Although merotelic attachments are common early in mitosis, some escape detection by the kinetochore pathway. As a consequence, a proportion of merotelic attachments gives rise to chromosome breakage in normal cells and in carcinomas. An intrinsic chromosome segregation defect might thus form the basis of tumor initiation. We propose a hypothesis in which merotelic attachments and chromosome breakage establish a feedback loop that results in relaxation of the spindle checkpoint and suppression of anti-proliferative pathways, thereby promoting carcinogenesis.
Multislice computed tomography is useful for evaluating partial anomalous pulmonary venous connection
Authors: Kasahara Hirofumi , Aeba Ryo , Tanami Yutaka , Yozu Ryohei
Published: May 2010

Volume-rendered images, derived from multidetector-row computed tomography (MDCT), can facilitate assessment of the morphology of partial anomalous pulmonary venous connection and are thus useful in pre-operative planning to prevent surgical morbidity and assist post-operative evaluations.
The roles of p38MAPK and caspase-3 in DADS-induced apoptosis in human HepG2 cells
Authors: Ji Chunxiao , Ren Fenglian , Ma Heng , Xu Ming
Published: May 2010

Objectives

To explore the function of p38MAPK and caspase-3 in DADS-induced apoptosis in human HepG2 cells, and discuss the signal transduetion mechanism of HepG2 cells in the apoptosis process induced by DADS by using the inhibitors of p38MAPK (SB203580) and caspase-3 (Z-DEVD-FMK).

Methods

After the human HepG2 cells had been treated with the DADS and inhibitors for 24 h, cell viability was determined by the MTT method, apoptosis was evaluated by flow cytometry (FCM) and the expressions of p38MAPK and caspase-3 were measured by western-blot.

Results

Our results indicated that DADS activities the p38MAPK and caspase-3, but the inhibitors, SB203580 and Z-DEVD-FMK (for p38MAPKand for caspase-3, respectively), both have the effect of inhibitory activity on P38MAPK and caspase-3. Furthermore, a combination treatment with both DADS and inhibitor (SB203580 or Z-DEVD-FMK) decreases the inhibitory and apoptotic activity of HepG2 cells increased compared with DADS-treated.

Conclusions

Our data indicate that p38MAPK and caspase-3 are involved in the process of DADS-induced apoptosis in human HepG2 cells and interact with each other.
Experimental stress in inflammatory rheumatic diseases: a review of psychophysiological stress responses
Authors: de Brouwer Sabine JM , Kraaimaat Floris W , Sweep Fred CGJ , Creemers Marjonne CW , Radstake Timothy RDJ , van Laarhoven Antoinette IM , van Riel Piet LCM , Evers Andrea WM
Published: May 2010

Introduction

Stressful events are thought to contribute to the aetiology, maintenance and exacerbation of rheumatic diseases. Given the growing interest in acute stress responses and disease, this review investigates the impact of real-life experimental psychosocial, cognitive, exercise and sensory stressors on autonomic, neuroendocrine and immune function in patients with inflammatory rheumatic diseases.

Methods

Databases Medline, PsychINFO, Embase, Cinahl and Pubmed were screened for studies (1985 to 2009) investigating physiological stress responses in inflammatory rheumatic diseases. Eighteen articles met the inclusion criteria.

Results

Results suggest that immune function may be altered in response to a stressor; such alterations could contribute to the maintenance or exacerbation of inflammatory rheumatic diseases during stressful events in daily life.

Conclusions

This review emphasizes the need for more experimental research in rheumatic populations with controlled stress paradigms that include a follow-up with multiple evaluation points, simultaneous assessment of different physiological stress systems, and studying factors contributing to specific physiological responses, such as stress appraisal.
Monocyte surface expression of Fcγ receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus
Authors: Li Yi , Lee Pui Y , Kellner Erinn S , Paulus Matthew , Switanek Juliana , Xu Yuan , Zhuang Haoyang , Sobel Eric S , Segal Mark S , Satoh Minoru , Reeves Westley H
Published: May 2010

Introduction

More than half of systemic lupus erythematosus (SLE) patients show evidence of excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection of IFN-I proteins in serum is unreliable, and the measurement of interferon-stimulated gene (ISG) expression is expensive and time consuming. The aim of this study was to identify a surrogate marker for IFN-I activity in clinical samples for monitoring disease activity and response to therapy.

Methods

Monocyte surface expression of Fcγ receptors (FcγRs), chemokine receptors, and activation markers were analyzed with flow cytometry in whole blood from patients with SLE and healthy controls. FcγR expression also was measured in peripheral blood mononuclear cells (PBMCs) from healthy controls cultured with Toll-like receptor (TLR) agonists, cytokines, or serum from SLE patients. Expression of ISGs was analyzed with real-time PCR.

Results

Circulating CD14+ monocytes from SLE patients showed increased surface expression of FcγRI (CD64). The mean fluorescent intensity of CD64 staining correlated highly with the ISG expression (MX1, IFI44, and Ly6E). In vitro, IFN-I as well as TLR7 and TLR9 agonists, induced CD64 expression on monocytes from healthy controls. Exposure of monocytes from healthy controls to SLE sera also upregulated the expression of CD64 in an IFN-I-dependent manner. Decreased CD64 expression was observed concomitant with the reduction of ISG expression after high-dose corticosteroid therapy.

Conclusions

Expression of CD64 on circulating monocytes is IFN-I inducible and highly correlated with ISG expression. Flow-cytometry analysis of CD64 expression on circulating monocytes is a convenient and rapid approach for estimating IFN-I levels in SLE patients.
Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus
Authors: Nie Ying J , Mok Mo Y , Chan Godfrey CF , Chan Albert W , Jin Ou , Kavikondala Sushma , Lie Albert KW , Lau Chak S
Published: May 2010

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T and B cells, which are believed to be secondary to deficient dendritic cells (DCs). However, whether DC abnormalities occur during their development in the bone marrow (BM) or in the periphery is not known.

Methods

Thirteen patients with SLE and 16 normal controls were recruited. We studied the morphology, phenotype, and functional abilities of bone marrow-derived dendritic cells (BMDCs) generated by using two culture methods: FMS-like tyrosine kinase 3 (Flt3)-ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), respectively.

Results

BMDCs induced by FL exhibited both myeloid (mDC) and plasmacytoid DC (pDC) features, whereas GM-CSF/IL-4 induced mDC generation. Substantial phenotypic and functional defects of BMDCs were found from patients with SLE at different stages of cell maturation. When compared with healthy controls, SLE immature BM FLDCs expressed higher levels of CCR7. Both immature and mature SLE BM FLDCs expressed higher levels of CD40 and CD86 and induced stronger T-cell proliferation. SLE BM mDCs expressed higher levels of CD40 and CD86 but lower levels of HLA-DR and a lower ability to stimulate T-cell proliferation when compared with control BM mDCs.

Conclusions

Our data are in accordance with previous reports that suggest that DCs have a potential pathogenic role in SLE. Defects of these cells are evident during their development in BM. BM mDCs are deficient, whereas BM pDCs, which are part of BM FLDCs, are the likely culprit in inducing autoimmunity in SLE.
Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis
Authors: Woo Jennifer MP , Lin Zhuofeng , Navab Mohamad , Van Dyck Casey , Trejo-Lopez Yvette , Woo Krystal MT , Li Hongyun , Castellani Lawrence W , Wang Xuping , Iikuni Noriko , Rullo Ornella J , Wu Hui , La Cava Antonio , Fogelman Alan M , Lusis Aldons J , Tsao Betty P
Published: May 2010

Introduction

The purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE-/-Fas-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet.

Methods

Female mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment.

Results

In preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (PL,LP< 0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (PL< 0.05) and oxidized phospholipids (oxPLs) (PL,LP< 0.005), and elevated total and vertebral bone mineral density (PL,LP< 0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68+macrophages (PLP< 0.01), significantly increased mean α-actin stained area (PLP< 0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (PL,LP< 0.0005) and VCAM-1 (PL< 0.0002).

Conclusions

L-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis.
Remission in psoriatic arthritis: is it possible and how can it be predicted?
Authors: Saber Tajvur P , Ng CT , Renard Guillaume , Lynch Bernadette M , Pontifex Eliza , Walsh Ceara AE , Grier Alexia , Molloy Marian , Bresnihan Barry , FitzGerald Oliver , Fearon Ursula , Veale Douglas J
Published: May 2010

Introduction

Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.

Methods

Analysis of a prospective patient cohort attending a biologic clinic, between November 2004 and March 2008, was performed prior to commencing therapy and at regular intervals. Baseline clinical characteristics including demographics, previous disease-modifying antirheumatic drug (DMARD) response, tender and swollen joint counts, early morning stiffness, pain visual analogue score, patient global assessment, C reactive protein (CRP) and health assessment questionnaire (HAQ) were collected.

Results

A total of 473 patients (152 PsA; 321 rheumatoid arthritis (RA)) were analyzed. At 12 months remission, defined according to the disease activity score using 28 joint count and CRP (DAS28-CRP), was achieved in 58% of PsA patients compared to 44% of RA patients, significant improvement in outcome measures were noted in both groups (P < 0.05). Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission. Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients (P < 0.001).

Conclusions

DAS28 remission is possible in PsA patients at one year following anti-TNF therapy, at higher rates than in RA patients and is predicted by baseline HAQ.
Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity
Authors: Davis Joshua S , Yeo Tsin W , Piera Kim A , Woodberry Tonia , Celermajer David S , Stephens Dianne P , Anstey Nicholas M
Published: May 2010

Introduction

Angiopoietin-2 (ang-2), an angiogenic peptide released by endothelial cell Weibel-Palade bodies (WPBs), increases endothelial activation and vascular permeability. Ang-2 is raised in severe sepsis but the mechanisms underlying this are not known. Nitric oxide (NO) inhibits WPB exocytosis, and bioavailability of endothelial NO is decreased in sepsis. We hypothesized that endothelial NO bioavailability would be inversely correlated with ang-2 concentrations in sepsis.

Methods

Plasma ang-2, vascular endothelial growth factor (VEGF) and endothelial-active cytokines were assessed in 83 patients with early sepsis and 41 hospital controls, and related to reactive hyperaemia-peripheral arterial tonometry, RH-PAT, a measure of endothelial NO bioavailability.

Results

Plasma Ang-2 was elevated in sepsis (median [interquartile range (IQR)], ng/ml: severe sepsis 12.4 [8.5-33.4], sepsis without organ failure 6.1 [5.0-10.4], controls 2.7 [2.2-3.6], P < 0.0001). It correlated inversely with RH-PAT (r = -0.38, P < 0.0001) and positively with IL-6 (r = 0.57, P < 0.0001) and degree of organ failure (sequential organ function assessment score) (r = 0.58, P < 0.0001). The correlation of ang-2 with RH-PAT persisted after controlling for sepsis severity. In a longitudinal mixed-effects model, recovery of RH-PAT over time was associated with decline in ang-2.

Conclusions

Ang-2 is elevated in proportion to sepsis severity, and inversely correlated with NO-dependent microvascular reactivity. Impaired endothelial NO bioavailability may contribute to increased endothelial cell release of ang-2, endothelial activation and capillary leak. Agents that increase endothelial NO bioavailability or inhibit WPB exocytosis and/or Ang-2 activity may have therapeutic potential in sepsis.
Starting an Adolescent and Young Adult Program: Some Success Stories and Some Obstacles to Overcome
Authors: Ferrari Andrea , Thomas David , Franklin Anna R.K. , Hayes-Lattin Brandon M. , Mascarin Maurizio , van der Graaf Winette , Albritton Karen H.
Published: May 2010

Adolescent and young adult (AYA) patients seem to be in a sort of no-man's land, halfway between the two different worlds of pediatric and adult medical oncology and bearing the brunt, in terms of inclusion in clinical trials and quality of professional care, of the lack of integration between these two worlds. This article discusses the different organization models of care used in pediatric oncology (mainly family-focused) and in adult medical oncology (disease-focused). There is a growing awareness that these models are not ideally suited to the complex needs of AYA patients, which require a different, new, patient-focused multidisciplinary approach. A comprehensive, multipronged effort is required to bridge the gap in the care of AYA patients, with the ultimate challenge of creating a new discipline, AYA oncology. In this article, we review the experiences of AYA oncology programs in Europe, North America, and Australia, focusing on similarities and differences in strategy, as well as the major challenges and opportunities faced by these programs. Among the most important factors for the successful establishment of an AYA oncology service are the degree of engagement of both pediatric and adult medical oncologists, the philanthropic support of powerful charities, and the role of dedicated professionals across a range of disciplines in driving the development of services for AYA patients.
Effective Reduction of Gastric Cancer Risk With Regular Use of Nonsteroidal Anti-Inflammatory Drugs in Helicobacter Pylori–Infected Patients
Authors: Wu Chun-Ying , Wu Ming-Shiang , Kuo Ken N. , Wang Chang-Bi , Chen Yi-Ju , Lin Jaw-Town
Published: May 2010

Purpose

Nonsteroidal anti-inflammatory drugs (NSAIDs) play protective roles in gastric carcinogenesis. However, the interaction between NSAIDs and Helicobacter pylori (H pylori) infection and the number needed to treat to prevent gastric cancer remains unclear.

Patients and Methods

We conducted a nationwide retrospective cohort study based on data from the Taiwan National Health Insurance Database. Hospitalized patients with a primary diagnosis of peptic ulcer disease were selected. Overall, 52,161 patients were divided into non-NSAID user and regular NSAID user cohorts. Standardized incidence ratios (SIRs), cumulative incidences, and hazard ratios (HRs) were calculated.

Results

Patients with peptic ulcers who never used NSAIDs had higher risk of gastric cancer compared with the general population (SIR, 2.11; 95% CI, 2.07 to 2.15), but regular NSAID use conferred lower risk (SIR, 0.79; 95% CI, 0.77 to 0.81). The protective role of NSAID use was observed in patients with gastric ulcer, but not in patients with non–H pylori-associated duodenal ulcer. On multivariate analysis, regular NSAID use was an independent protective factor for gastric cancer development (HR, 0.79 for each incremental year; P < .001), especially in H pylori-associated patients (HR, 0.52 for each incremental year; P < .001). Among patients with H pylori-infected gastric ulcers, the NNT to prevent a gastric cancer was 50.

Conclusion

Regular NSAID use may be a feasible way to prevent gastric cancer, at least in patients with gastric ulcers, and especially in H pylori-infected subjects.
Akt Phosphorylation at Ser473 Predicts Benefit of Paclitaxel Chemotherapy in Node-Positive Breast Cancer
Authors: Yang Sherry X. , Costantino Joseph P. , Kim Chungyeul , Mamounas Eleftherios P. , Nguyen Dat , Jeong Jong-Hyeon , Wolmark Norman , Kidwell Kelley , Paik Soonmyung , Swain Sandra M.
Published: May 2010

Purpose

We tested the hypothesis that Akt-Ser473 phosphorylation (pAkt) predicts benefit from the sequential addition of paclitaxel to adjuvant doxorubicin plus cyclophosphamide (AC) chemotherapy in patients with node-positive breast cancer participating in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 trial.

Patients and Methods

Primary tumors from the NSABP B-28 trial tissue microarray were available from 1,581 of 3,060 patients who were randomly assigned to receive either four cycles of AC alone or followed by four cycles of paclitaxel. Immunohistochemistry and quantitative analysis of pAkt were performed at the National Cancer Institute blinded to clinical outcome. Association between pAkt and clinical outcome was assessed using multivariate Cox modeling adjusting for age, tumor size, number of positive nodes, tumor grade, estrogen receptor status, and human epidermal growth factor receptor 2 status.

Results

With a median follow-up of 9.1 years, there were no differences in disease-free survival (adjusted hazard ratio [HR], 1.02; P = .81) or overall survival (HR, 0.97; P = .80) with and without receiving paclitaxel among 975 patients with pAkt-negative tumors. In 606 patients with pAkt-positive tumors, the sequential addition of paclitaxel resulted in a 26% improvement in disease-free survival (HR, 0.74; P = .02) or a 20% improvement in overall survival (HR, 0.80; P = .17).

Conclusion

pAkt significantly predicts disease-free benefit from the sequential addition of paclitaxel to AC chemotherapy in patients with node-positive breast cancer. Patients with pAkt-negative breast tumors do not appear to benefit from the addition of paclitaxel.
Longitudinal Study of Depressive Symptoms in Patients With Metastatic Gastrointestinal and Lung Cancer
Authors: Lo Christopher , Zimmermann Camilla , Rydall Anne , Walsh Andrew , Jones Jennifer M. , Moore Malcolm J. , Shepherd Frances A. , Gagliese Lucia , Rodin Gary
Published: May 2010

Purpose

Although early intervention is increasingly advocated to prevent and relieve distress in patients with metastatic cancer, the risk factors for such symptoms and their trajectory are not well established. We therefore conducted a longitudinal study to determine the course and predictors of depressive symptoms.

Patients and Methods

Patients (N = 365) with metastatic gastrointestinal or lung cancer completed measures of physical distress, self-esteem, attachment security, spiritual well-being, social support, hopelessness, and depression at baseline; physical distress, social support, hopelessness, and depression were subsequently assessed at 2-month intervals.

Results

Of the sample, 35% reported at least mild depressive symptoms, with 16% reporting moderate to severe depressive symptoms that persisted in at least one third of such individuals. Moderate to severe depressive symptoms were almost three times more common in the final 3 months of life than ≥ 1 year before death. Predictors of depressive symptoms included younger age, antidepressant use at baseline, lower self-esteem and spiritual well-being, and greater attachment anxiety, hopelessness, physical burden of illness, and proximity to death. The combination of greater physical suffering and psychosocial vulnerability put individuals at greatest risk for depression.

Conclusion

Depressive symptoms in advanced cancer patients are relatively common and may arise as a final common pathway of distress in response to psychosocial vulnerabilities, physical suffering, and proximity to death. These findings support the need for an integrated approach to address emotional and physical distress in this population and to determine whether early intervention may prevent depression at the end of life.
Genetic Testing in Li-Fraumeni Syndrome: Uptake and Psychosocial Consequences
Authors: Lammens Chantal R.M. , Aaronson Neil K. , Wagner Anja , Sijmons Rolf H. , Ausems Margreet G.E.M. , Vriends Annette H. J.T. , Ruijs Mariëlle W.G. , van Os Theo A.M. , Spruijt Liesbeth , Gómez García Encarna B. , Kluijt Irma , Nagtegaal Tanja , Verhoef Senno , Bleiker Eveline M.A.
Published: May 2010

Purpose

Li-Fraumeni syndrome (LFS) is a hereditary cancer syndrome, characterized by a high risk of developing cancer at various sites and ages. To date, limited clinical benefits of genetic testing for LFS have been demonstrated, and there are concerns about the potential adverse psychosocial impact of genetic testing for LFS. In this study, we evaluated the uptake of genetic testing and the psychosocial impact of undergoing or not undergoing a genetic test for LFS.

Patients and Methods

In total, 18 families with a p53 germline mutation in the Netherlands were identified. Eligible family members were invited to complete a self-report questionnaire assessing motives for undergoing or not undergoing genetic testing, LFS-related distress and worries, and health-related quality of life.

Results

Uptake of presymptomatic testing was 55% (65 of 119). Of the total group, 23% reported clinically relevant levels of LFS-related distress. Carriers were not significantly more distressed than noncarriers or than those with a 50% risk who did not undergo genetic testing. Those with a lack of social support were more prone to report clinically relevant levels of distress (odds ratio, 1.3; 95% CI, 1.0 to 1.5).

Conclusion

Although preventive and treatment options for LFS are limited, more than half of the family members from known LFS families choose to undergo presymptomatic testing. An unfavorable genetic test result, in general, does not cause adverse psychological effects. Nonetheless, it is important to note that a substantial proportion of individuals, irrespective of their carrier status, exhibit clinically relevant levels of distress which warrant psychological support.
Evaluation of the Value of Attribution in the Interpretation of Adverse Event Data: A North Central Cancer Treatment Group and American College of Surgeons Oncology Group Investigation
Authors: Hillman Shauna L. , Mandrekar Sumithra J. , Bot Brian , DeMatteo Ronald P. , Perez Edith A. , Ballman Karla V. , Nelson Heidi , Buckner Jan C. , Sargent Daniel J.
Published: May 2010

Purpose

In March 1998, Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AEs) to study drug. We investigate whether attribution adds value to the interpretation of AE data.

Patients and Methods

Patients in the placebo arm of two phase III trials—North Central Cancer Treatment Group Trial 97-24-51 (carboxyamino-triazole v placebo in advanced non–small-cell lung cancer) and American College of Surgeons Oncology Group Trial Z9001 (imatinib mesylate v placebo after resection of primary gastrointestinal stromal tumors)—were studied. Attribution was categorized as unrelated (not related or unlikely) and related (possible, probable, or definite).

Results

In total, 398 patients (84 from Trial 97-24-51 and 314 from Trial Z9001) and 7,736 AEs were included; 47% and 50% of the placebo-arm AEs, respectively, were reported as related. When the same AE was reported in the same patient on multiple visits, the attribution category changed at least once 36% and 31% of the time. AE type and sex (Trial Z9001) and AE type and performance status (Trial 97-24-51) were associated with a higher likelihood of AEs being deemed related.

Conclusion

Nearly 50% of AEs were reported as attributed to study drug on the placebo arm of two randomized clinical trials. These data provide strong evidence that AE attribution is difficult to determine, unreliable, and of questionable value in interpreting AE data in randomized clinical trials.
Critical Impact of Radiotherapy Protocol Compliance and Quality in the Treatment of Advanced Head and Neck Cancer: Results From TROG 02.02
Authors: Peters Lester J. , O'Sullivan Brian , Giralt Jordi , Fitzgerald Thomas J. , Trotti Andy , Bernier Jacques , Bourhis Jean , Yuen Kally , Fisher Richard , Rischin Danny
Published: May 2010

Purpose

To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer.

Patients and Methods

The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality.

Results

At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; ≥ 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): −2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively.

Conclusion

These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.
Moroccan Migrants in Europe and Islamophobia
Authors: Ennaji Moha
Published: May 2010

The major aspiration of Moroccan migrants was, and remains, the realization of their migration project, which is the improvement of their well-being and that of their families. Over the years, the migration project led to the emergence of a nuclear family in the host country, constituting a key component of the migratory situation and engendering challenges for migrants and their children, as well as for the receiving and sending countries. In general, three major features characterize the situation of Moroccan migrants: (1) the first and second generations face social segregation and experience loneliness and homesickness; (2) children are drawn between the culture of the country of origin and that of the host country, a dilemma they themselves have to resolve; and (3) immigrants are subject to the Islamophobia that results from the presumption that Islam is a totalitarian religion that is incompatible with the European (and Western) values of freedom of religion, equality, human rights, and democracy. Multiculturalism and cultural diversity may be considered means for integration and devices for bringing about or preserving cultural, religious, racial, ethnic, linguistic diversity. Multiculturalism, or some form of it, could be invoked by such a host country to promote diversity and discourage homogenizing activities.
A Name Given, a Name Taken: Camouflaging, Resistance, and Diasporic Social Identity
Authors: Spitzer Leo
Published: May 2010

Naming a person makes him or her a part of the social world—a name gives the person a social identity. At the same time, a name stands for the person, it symbolizes personal identity. It indicates to members of society who the named one is and, to the named one, who he or she is expected to be. Comparing naming practices and name acquisition by blacks and Jews in British colonial West Africa and Central Europe during the century of emancipation from the 1780s to the 1860s, and during the subsequent era of growing exclusionist racism and anti-Semitism, this essay examines being given a name and taking or changing a name as acts of identification, differentiation, camouflaging, and resistance.
Sufis on Exile and Ghorba: Conceptualizing Displacement and Modern Subjectivity
Authors: El Khachab Walid
Published: May 2010

Sufis' theory of ghorba (estrangement or exile) underlies here a reflection on exile in contemporary Arab cultures. Hence Ibn al-Arabi's speculations on ghorba in Al-Futuhat al-Makkiyya shed a new light on Arjun Appadurai's notion of “ethnoscape.” The Sufi concept of ghorba paves the way for a modern Arab ethnoscape, where the Arab subject experiences transnational movement in the global space without associating this experience with the negative aspects of exile.

Ibn al-Arabi dismisses the negative effects of “geographic” displacement. According to his reasoning, an expatriate does not feel estranged anywhere he or she travels, since the world—and the divine—are in continuity with the human subject. The real exile is a psychological experience resulting from the disruption of monist unity and harmony between human and divine, man and the world.

This conception of exile challenges nationalist theories of estrangement based on the assumption that a sense of displacement is bound to physical movement out of the national territory. Ghorba is a state in which the subject is far from his or her ethical and spiritual plenitude (thanks to the Sufi mystical unity with the divine), not a geopolitical situation. This conception challenges the dogmatic distinction of House of Islam versus House of War in Arab Islamic Sunni tradition, where the displacement out of the former results in an experience of exile.

In modern terms, ghorba—as conceptualized by Sufis—provides a traditional basis helping the modern Arab subject cope with the experience of displacement, by shifting the paradigm of belonging from the realm of geopolitics to that of spirituality and ethics. Thus the construction of a modern postnational Arab subjectivity can be achieved thanks to the investment of the ethnoscape—a virtual space that transcends national boundaries but keeps active a network of affects and cultural references and products unifying an ethnically distinct subject. The Sufi sense of belonging to the whole world makes it politically and ethically acceptable to feel at home outside of one's homeland, without being stripped from one's ethnicity. It adds to this compromise a dimension of spiritual fulfillment, since the horizontal ethnoscape intersects with a vertical spiritual axis, constantly neutralizing nostalgia to the geographic paradise of origins.
Sclerotherapy of voluminous venous malformation in head and neck with absolute ethanol under digital subtraction angiography guidance
Authors: Wang Y A , Zheng J W , Zhu H G , Ye W M , He Y , Zhang Z Y
Published: May 2010

Objectives

Venous malformation (VM) is the most common symptomatic low-flow vascular malformation, which predominantly occurs in the head and neck region. The aim of this paper was to evaluate the results of endovascular sclerotherapy of voluminous VM, when the lesion is either ≥15 cm in maximum diameter or the lesion invades more than one anatomical space, in the head and neck region using absolute ethanol under digital subtraction angiography (DSA) guidance.

Methods

A total of 23 patients with head and neck VMs between October 2005 and December 2008 were retrospectively reviewed. All patients received direct puncture ethanol sclerotherapy under DSA guidance. Follow-up assessments were performed at 3–25 months after therapies were completed, and complications were reported in some cases.

Results

All patients were satisfied with the results of therapy. Seventeen patients (73.9%) achieved excellent responses and six patients (26.1%) achieved good responses in magnetic resonance imaging assessments. Minor complications developed during the procedures, all of which were successfully managed with full recovery during follow-ups. Serious complications such as acute pulmonary hypertension, cardiovascular collapse and pulmonary embolism were not encountered.

Conclusion

It is concluded that sclerotherapy with absolute ethanol under DSA guidance is an important alternative therapy for voluminous and extensive VM, as the procedure is reasonably safe and offers good therapeutic results.