bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital Midgut Volvulus Associated with Fetal Anemia
Authors: Kornacki Jakub , Czarnecka Monika , Błaszczyński Michał , Skrzypczak Jana , Gadzinowski Janusz , Jankowski Andrzej , Sardesai Smeeta
Published: August 2010

Congenital volvulus is a life-threatening condition, both for the fetus and for the newborn. A volvulus is a twist of small bowel loops or a proximal part of the colon around the mesenteric artery or its branches. The potential consequences of volvulus are ileus and necrosis of the intestinal wall. Prenatal diagnosis of midgut volvulus is difficult. It should be suspected antenatally when polyhydramnios, intestinal dilatation, ascites and/or signs of fetal anemia are present on ultrasound assessment. We report a case of a congenital midgut volvulus associated with fetal anemia. The fetal ultrasound performed at 32 weeks’ gestation showed a polyhydramnios, hydrothorax, thick ascites accumulation around the liver and the suspicion of a dilated bowel loop. Additionally, Doppler examination showed an increased value of peak systolic velocity in the middle cerebral artery. Cordocentesis confirmed significant fetal anemia. At 34 weeks, because of the suspicion of idiopathic meconium ileus and secondary anemia, a Cesarean section was performed after the administration of steroids. During the laparatomy, performed postnatally, a midgut volvulus was diagnosed. The affected portion of the ileum was resected and end-to-end anastomosis performed. An antenatal diagnosis of midgut volvulus should be considered when signs of fetal anemia, including an increased value of peak systolic velocity in the middle cerebral artery, are present with polyhydramnios, fetal ascites, dilated bowel loops on antenatal ultrasound. An assessment of the fetal hemodynamic status should be a part of the ultrasound assessment for patients with nonspecific fetal bowel pathologies, including congenital volvulus.
Effects of Antenatal Steroid Therapy on Neurodevelopment in an IUGR Mouse Model
Authors: Velayo Clarissa , Ito Takuya , Chisaka Hiroshi , Yaegashi Nobuo , Okamura Kunihiro , Kimura Yoshitaka
Published: August 2010

Background/Objective: To investigate the neurodevelopmental response in postnatal mice secondary to antenatal steroid treatment in association with maternal protein restriction. Methods: C57BL/6N pregnant mice (n = 24; 4 per treatment group) were administered control (C) or protein-restricted (PR) diets and subjected to daily subcutaneous injection stress during late gestation (E10–E17) with either 100 µl/kg of dexamethasone sodium phosphate in normosaline (C-D/S, PR-D/S) or normosaline alone (C-S, PR-S). Non-treatment groups were also included (C, PR). Brain samples of pups were collected on postnatal day 7 and analyzed by immunohistochemistry and qRT-PCR. Results: Neonatal weights in the treatment groups were smaller than their counterparts in the C group, but there were no significant differences in brain size. Immunohistochemical evaluation of neuroglial cells revealed a pronounced effect of protein restriction on oligodendrocytes and oligodendrocyte precursor cells with distinct fetal responses to stress and dexamethasone. Further evaluation using quantitative RNA analysis showed significant activation of Galr1, Galr2, Igfbp-1, Igfbp-3, Igfbp-6, and Fgf2 by 1- to 2.5-fold in the PR-D/S group and by much higher increments, 1- to 10.5-fold, in the PR-S group. Conclusion: This preliminary investigation revealed the possible role of dexamethasone in further increasing vulnerability to cell damage in injury-prone neuroglial cells. The distribution of key glial markers and the overexpression of several neurotrophic factors depicted ongoing cellular adaptation.
The Burden of Nail Psoriasis: An Introduction
Authors: Baran Robert
Published: August 2010

Nail involvement is an extremely common feature of psoriasis and affects approximately 50% of patients. Despite this, it is an often overlooked feature of the disease, and treatment tends to be focused on clearing the cutaneous component of psoriasis. Clinical manifestations of nail psoriasis are pitting, discolouration, onycholysis and subungual hyperkeratosis as well as nail plate crumbling and splinter haemorrhages. Nail psoriasis is associated with discomfort in many patients and leads to significant functional impairment and psychological stress. The often distressing appearance of affected nails impacts the patient tremendously in both work and social activities. Importantly, 80% of patients with psoriatic arthritis have nail psoriasis. This review discusses the incidence of nail psoriasis and the burden on the patient and illustrates when dermatologists are strategically placed to detect the early signs of more severe disease by promptly diagnosing and managing the nail component of psoriasis.
Trisomy 16 Mosaicism at Chorionic Villus Sampling and Amniocentesis with a Normal Physical and Intellectual Outcome
Authors: Coman D. , Gardner R.J.M. , Pertile M.D. , Kannu P.
Published: August 2010

The identification of trisomy mosaicism in the prenatal setting is often shrouded with uncertainty for the genetic counsellor, and more importantly for the parents. The outcomes for these pregnancies may well be normal, but abnormalities and even in utero death are possibilities depending on the chromosomal abnormality and the degree of mosaicism. Advice to parents following the diagnosis of trisomy 16 mosaicism at chorionic villus sampling, with confirmation at subsequent amniocentesis, and in the setting of apparently normal fetal ultrasonography, is necessarily cautious. Malformations are seen in the majority of infants born following a diagnosis of mosaic trisomy 16 at amniocentesis, and intrauterine growth retardation, with postnatal catch-up, is the rule. We report here a case with a normal outcome by age 2.5 years and in fact with above-average language ability, and in whom trisomy mosaicism was confirmed postnatally.
Volume Not Guaranteed: Closed Endotracheal Suction Compromises Ventilation in Volume-Targeted Mode
Authors: Kiraly Nicholas J. , Tingay David G. , Mills John F. , Dargaville Peter A. , Copnell Beverley
Published: August 2010

Background: Closed endotracheal suction interferes with mechanical ventilation received by infants, but the change to ventilation may be different when ventilator modes that target expired tidal volume (VTe) are used. Objective: To measure airway pressure and tidal volume distal to the endotracheal tube (ETT) during and after closed suction in a volume-targeted ventilation mode with the Dräger Babylog 8000+, and to determine the time until VTe returns to the baseline level. Methods: In this benchtop study, closed suction was performed on 2.5- to 4.0-mm ETTs connected to a test lung. 5–8 French suction catheters were used at suction pressures of 80–200 mm Hg during tidal-volume-targeted ventilation. Results: During catheter insertion and suction, circuit inflating pressure increased and tidal volume was maintained, except when a large catheter relative to the ETT was used, in which case tidal volume decreased. End-expiratory pressure distal to the ETT was reduced during suction by up to 75 cm H2O while circuit end-expiratory pressure was unchanged. Reduction in end-expiratory pressure distal to the ETT was greatest with large catheters and high suction pressures. Following suction, circuit and tracheal inflating pressures increased and tidal volume increased before returning to baseline in 8–12 s. Conclusions: Closed endotracheal suction interferes with ventilator function in volume-targeted mode, with substantially negative intratracheal pressure during suction, and the potential for high airway pressures and tidal volumes following the procedure. These effects should be considered and pressure limits set appropriately whenever using volume-targeted ventilation.
Utility of Early MRI in the Diagnosis and Management of Acute Spontaneous Intracerebral Hemorrhage
Authors: Wijman Christine A.C. , Venkatasubramanian Chitra , Bruins Sara , Fischbein Nancy , Schwartz Neil
Published: August 2010

Background: The optimal diagnostic evaluation for spontaneous intracerebral hemorrhage (ICH) remains controversial. In this retrospective study, we assessed the utility of early magnetic resonance imaging (MRI) in ICH diagnosis and management. Methods: Eighty-nine (72%) of 123 patients with spontaneous ICH underwent a brain CT and MRI within 30 days of ICH onset. Seventy patients with a mean age of 62 ± 15 years were included. A stroke neurologist and a general neurologist, each blinded to the final diagnosis, independently reviewed the admission data and the initial head CT and then assigned a presumed ICH cause under 1 of 9 categories. ICH cause was potentially modified after subsequent MRI review. The final ‘gold standard’ ICH etiology was determined after review of the complete medical record by an independent investigator. Change in diagnostic category and confidence and the potential impact on patient management were systematically recorded. Results: Mean time to MRI was 3 ± 5 days. Final ICH diagnosis was hypertension or cerebral amyloid angiopathy (CAA) in 50% of patients. After MRI review the stroke neurologist changed diagnostic category in 14%, diagnostic confidence in an additional 23% and management in 20%, and the general neurologist did so in 19, 21 and 21% of patients, respectively. MRI yield was highest in ICH secondary to ischemic stroke, CAA, vascular malformations and neoplasms, and did not differ by age, history of hypertension, hematoma location or the presence of intraventricular hemorrhage. Conclusions: The results of this study suggest potential additive clinical benefit of early MRI in patients with spontaneous ICH.
Case Report and Review: Prenatal Diagnosis of Congenital Megalourethra
Authors: Promsonthi Patama , Viseshsindh Wit
Published: August 2010

Megalourethra is a rare congenital anomaly characterized by dilatation of the penile urethra which causes functional obstruction of the lower urinary system. We present a case of congenital megalourethra diagnosed prenatally. Transabdominal sonography revealed a male fetus with bilateral hydroureter, hydronephrosis, dilated bladder and normal amniotic fluid. The fetal penis was enlarged and the penile urethra was dilated with ballooning at the distal end. The urethral meatus was identified. The fetus was delivered at term with a favorable outcome.
Laryngeal Tremor: Co-Occurrence with Other Movement Disorders
Authors: Wolraich D. , Vasile Marchis-Crisan C. , Redding N. , Khella S.L. , Mirza N.
Published: August 2010

Introduction: Limited epidemiologic information exists regarding the co-occurrence of laryngeal tremor (LT) and tremor in other parts of the body, and of other movement disorders. Tremor is the involuntary skeletal muscle contraction that leads to oscillatory movement. It can affect many parts of the body including the chin, neck, laryngeal muscles, or limbs. When it is not associated with parkinsonism, it is called an essential tremor. We reviewed our 5-year experience with LT patients and the presence of other movement disorders. Methods: We performed a retrospective review of 29 patients with LT seen in a voice clinic over a 5-year period from January 2004 to April 2009. Results: Of the 29 patients, 27 (93%) had co-incidence of another movement disorder. Of these patients, 45% had spasmodic dysphonia, 41% had oropharyngeal tremors, 38% had essential limb tremor, 31% had orofacial dystonias, and 24% had essential head and neck tremor. Only 1 patient (3%) presented with Parkinson’s disease. Conclusion: Otolaryngologists may be the first to evaluate a patient for tremors. It is important to consider other movement disorders when examining these patients as neurologic assessment and treatment of other tremors may be beneficial.
Level of Albuminuria and Risk of Stroke: Systematic Review and Meta-Analysis
Authors: Lee Meng , Saver Jeffrey L. , Chang Kuo-Hsuan , Ovbiagele Bruce
Published: August 2010

Background: Gross albuminuria is associated with increased stroke risk, but it is unclear whether stroke incidence varies by level of albuminuria. We meta-analyzed prospective cohort studies to investigate the impact of various albuminuria levels and continuous urinary albumin excretion (UAE) change on stroke risk. Methods: Systematic search for studies reporting quantitative estimates of the multivariate-adjusted relative risk (RR) and 95% CI for stroke risk associated with microalbuminuria (UAE 30–300 mg/day or nearest equivalent interval) and macroalbuminuria (UAE >300 mg/day) and studies that analyzed the relation of stroke with UAE continuously. Estimates were combined using a random-effect model. Results: We identified seven studies comprising 46,638 participants with 1,479 stroke events. Incident stroke risk was greater for macroalbuminuria (RR 2.65, 95% CI 2.25–3.14) than microalbuminuria (RR 1.58, 95% CI 1.39–1.80), a difference that was significant (p for heterogeneity < 0.001, I2 = 96%). In addition, risk of stroke increased proportionally with rising UAE (p < 0.001), even for UAE within normal range (beginning from levels as low as 2–4 mg/g). Conclusions: Higher albuminuria level confers greater stroke risk. These findings provide additional weight to evidence that albuminuria is strongly linked to stroke risk, and suggest that persons with elevated UAE levels may especially benefit from more intensive vascular risk reduction.
Gender Differences in Outcomes after Ischemic Stroke: Role of Ischemic Lesion Volume and Intracranial Large-Artery Occlusion
Authors: Silva Gisele S. , Lima Fabricio O. , Camargo Erica C.S. , Smith Wade S. , Lev Michael H. , Harris Gordon J. , Halpern Elkan F. , Koroshetz Walter , Furie Karen L.
Published: August 2010

Background: The reasons for gender disparities in stroke outcome remain unclear, and little is known about the value of acute neuroimaging characteristics in elucidating differential stroke outcomes between the sexes. Methods: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography (CTA) was performed in all patients within 24 h of symptom onset. CTA source images were used to evaluate lesion volume. The primary outcome measure was a modified Rankin scale (mRS) score ≧3 at 6 months. Results: We evaluated 676 consecutive patients (322 women). Women were older than men (p < 0.01), more frequently had a prestroke mRS >0 (p < 0.01), and had higher admission National Institutes of Health Stroke scale scores (p = 0.01). More women had intracranial artery occlusions than men (46 vs. 33.1%, p = 0.01), but there was no significant difference between ischemic lesion volumes (p = 0.21). Using multiple regression, female gender remained an independent predictor of poor mRS scores at 6 months (odds ratio 1.57; 95% confidence interval 1.02–2.36) after adjustment for clinical and imaging covariates. Conclusion: Compared with men, women are less likely to achieve independence after acute ischemic stroke. The disparity in stroke outcome is not explained by differences in ischemic lesion volume or the presence of intracranial artery occlusions.
Neural Tube Defects: Review of Experimental Evidence on Stem Cell Therapy and Newer Treatment Options
Authors: Dhaulakhandi Dhara B. , Rohilla Seema , Rattan Kamal Nain
Published: August 2010

The failure of closure of the neural tube during development leads to malformations called neural tube defects (NTDs). The most common neural malformations in humans include anencephaly, encephalocele, exencephaly, craniorachischisis spina bifida with or without myelomeningocele, lipomyeloschisis, lipomyelomeningocele, meningocele and myelocystocele. Current preventive strategies are mainly based on pharmacologic/folic acid supplementation. However, stem cell-based and other combination approaches may emerge as potential treatment options for NTDs. This review provides an account of experimental evidence on stem cell therapy and newer treatment options for NTDs which have become available in recent years.
Small Cell Carcinoma of the Esophagus Treated with Esophagectomy and following Chemotherapy: Case Report with Review of the Literature
Authors: Usami S. , Motoyama S. , Maruyama K. , Sato Y. , Shibuya K.H. , Nakatsu T. , Saito H. , Minamiya Y. , Ogawa J.
Published: August 2010

We report 2 cases of small cell carcinoma of the esophagus treated with esophagectomy as a primary treatment and following chemotherapy. One patient (pT1N1M0) achieved long-term survival, while the other patient (pT1N1M1-lym) died 18 months after surgery. We used reports on 47 Japanese patients receiving esophagectomy as a primary treatment to determine when esophagectomy for small cell carcinoma of the esophagus is indicated. We conclude that esophagectomy as a local treatment provides relatively good long-term survival only in patients without lymph node involvement.
Voxel-Based Analysis of Amyloid Positron Emission Tomography Probe [11C]BF-227 Uptake in Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Shao He , Okamura Nobuyuki , Sugi Kentaro , Furumoto Shozo , Furukawa Katsutoshi , Tashiro Manabu , Iwata Ren , Matsuda Hiroshi , Kudo Yukitsuka , Arai Hiroyuki , Fukuda Hiroshi , Yanai Kazuhiko
Published: August 2010

Aim: To determine early brain changes in the distribution of an amyloid positron emission tomography (PET) probe, 11C-labeled BF-227 or [11C]BF-227, in order to accurately predict the progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Patients and Methods: Amyloid plaque burden was evaluated using [11C]BF-227 PET in AD, MCI and aged normal controls. A voxel-based analysis of [11C]BF-227 PET images was performed to characterize the culprit brain lesion in patients with MCI who were destined to progress to AD, referred to as MCI converters (MCI-C). In addition, binding characteristics of BF-227 to amyloid deposits were examined using postmortem AD brain samples. Results: Voxel-based statistical analyses of the BF-227 PET images clearly demonstrated an abnormal distribution of BF-227 mainly in the posterior association area in MCI-C and patients with AD. BF-227 uptake in the lateral temporal cortex was consistently observed in almost all MCI-C and patients with AD, and it distinguished MCI-C from MCI nonconverters. BF-227 binding strongly correlated with dense amyloid-β protein plaque density, but not with diffuse plaque density in the frontal cortex. Conclusion: BF-227 uptake in the lateral temporal cortex is a reliable indicator that can be used for predicting prognosis in patients with MCI.
Delirium Is Not Associated with Mortality in Elderly Hip Fracture Patients
Authors: Juliebø Vibeke , Krogseth Maria , Skovlund Eva , Engedal Knut , Ranhoff Anette H. , Wyller Torgeir Bruun
Published: August 2010

Background: The relationship between delirium and mortality remains obscure. The aims of this study were to investigate the effect of delirium and the interaction between delirium and chronic cognitive impairment on mortality in elderly hip fracture patients. Methods: This is a prospective observational study, including 331 hip fracture patients. Information on comorbidity, medications and clinical findings was collected at the time of fracture. Information on cause and time of death was obtained from the Norwegian Cause of Death Register. Patients were screened for delirium by the Confusion Assessment Method. Results: Delirium was not associated with mortality when adjusting for the severity of chronic cognitive impairment, measured by the Infor- mant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Estimated by Kaplan-Meier plots, delirium in patients with dementia was significantly associated with an increased risk of death from stroke (p = 0.004) and dementia (p ≤ 0.001). Conclusions: No association between delirium and mortality was demonstrated when adjusting for the IQCODE score, but delirium in patients with prefracture dementia was associated with an increased risk of death from stroke and dementia. The effect of delirium on the cause of death might be explained by an aggravation of an ongoing neuro-inflammation.
Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study
Authors: Gold Michael , Alderton Claire , Zvartau-Hind Marina , Egginton Sally , Saunders Ann M. , Irizarry Michael , Craft Suzanne , Landreth Gary , Linnamägi Ülla , Sawchak Sharon
Published: August 2010

Background/Aims: A phase II study of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer’s disease (AD) detected a treatment benefit to cognition in apolipoprotein E(APOE)-Ε4-negative subjects. The current phase III study with prospective stratification by APOE genotype was conducted to confirm the efficacy and safety of RSG XR in mild-to-moderate AD. An open-label extension study assessed the long-term safety and tolerability of 8 mg RSG XR. Methods: This double-blind, randomized, placebo-controlled study enrolled 693 subjects. Within 2 APOE allelic strata (Ε4-positive, Ε4-negative), subjects were randomized (2:2:2:1) to once-daily placebo, 2 mg RSG XR, 8 mg RSG XR or 10 mg donepezil (control). Coprimary endpoints were change from baseline to week 24 in the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) score, and week 24 Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC+). Results: At week 24, no significant differences from placebo in change from baseline in coprimary endpoints were detected with either the RSG XR dose in APOE-Ε4-negative subjects or overall. For donepezil, no significant treatment difference was detected in ADAS-Cog; however, a significant difference was detected (p = 0.009) on the CIBIC+. Peripheral edema was the most common adverse event for 8 mg RSG XR (15%) and placebo (5%), and nasopharyngitis for 2 mg RSG XR (7%). Conclusion: No evidence of efficacy of 2 mg or 8 mg RSG XR monotherapy in cognition or global function was detected in the APOE-Ε4-negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology.
Long-Term Evaluation of Cochlear Implantation in Cogan Syndrome
Authors: Kontorinis Georgios , Giourgas Alexandros , Neuburger Juergen , Lesinski-Schiedat Anke , Lenarz Thomas
Published: August 2010

Purpose: The evaluation of long-term results of cochlear implantation in patients with typical Cogan syndrome. Procedures: The medical records of approximately 3,000 patients who underwent cochlear implantation in a tertiary centre within the period 1992–2007 were retrospectively examined. Results: Four cochlear implant recipients with Cogan syndrome (6 implantations) were identified. One cochlea was found to be partially obliterated; the electrode could, however, be completely inserted. Wound healing disorders and infections in a patient with systemic symptoms were the only postoperative complications. Hearing outcome was favorable, with average HSM and monosyllabic scores of 96.7 and 82.5%, respectively, in an average follow-up time of 9.25 years. Conclusions: Cochlear implantation is the appropriate hearing rehabilitation method in Cogan syndrome patients. Although the basic illness does not affect the long-term hearing outcome, skin-atrophy-related complications in cases with systemic symptoms may occur. Finally, the cochlear implant surgeon should be aware of the possible cochlea obliteration.
Drug Rash with Eosinophilia and Systemic Symptoms due to Telaprevir
Authors: Montaudié H. , Passeron T. , Cardot-Leccia N. , Sebbag N. , Lacour J.P.
Published: August 2010

We report a case of drug rash with eosinophilia and systemic symptoms (DRESS) due to telaprevir (VX-950), a specific inhibitor of the hepatitis C virus (HCV) serine protease. A 57-year-old woman with chronic hepatitis C was included in a phase 2 rollover study of VX-950. She received VX-950 in combination with pegylated interferon alfa-2a and ribavirin. Six weeks later, she developed a generalized pruritic maculopapular exanthema with malaise, fever, dyspnoea and lymph node swelling. She had an eosinophilia (up to 2.7 × 109 cells/l), large activated lymphocytes and increased concentrations of aminotransferases. Histological examination of a cutaneous biopsy was consistent with a drug rash reaction. The HCV treatment was stopped, and she was treated with topical and oral steroids. Cutaneous and systemic symptoms disappeared within 1 month. Telaprevir was considered the culprit drug. We report to our knowledge the first case of DRESS syndrome due to telaprevir. The safety data of telaprevir is derived mainly from the PROVE1, PROVE2 and PROVE3 studies. They showed a high frequency of cutaneous side effects reported under the imprecise terms of pruritus and rash, leading to an increased rate of treatment discontinuation. Telaprevir, due to its efficacy, is probably on the way to obtaining regulatory approval in the near future. It is therefore important to be aware of the high incidence of cutaneous side effects and better describe them. Our observation suggests that potentially severe hypersensitivity reactions may belong to the spectrum of rashes induced by this drug.
Genetic Variants in the C-Reactive Protein Gene Are Associated with Microangiopathic Ischemic Stroke
Authors: Kuhlenbaeumer Gregor , Huge Andreas , Berger Klaus , Kessler Christof , Voelzke Henry , Funke Harald , Stoegbauer Florian , Stoll Monika , Ringelstein E. Bernd
Published: August 2010

Background and Purpose: C-reactive protein (CRP) is an independent risk factor for cardiovascular disease and ischemic stroke. CRP serum levels are influenced by genetic variation in the CRP gene. Studies investigating the relationship between ischemic stroke and polymorphisms in the CRP gene produced equivocal results. Here we investigate single-nucleotide polymorphisms (SNPs) in the CRP gene in a large German ischemic stroke sample. Methods: In a case-control design, 1,669 patients with ischemic stroke due to large-artery atherosclerosis, cardioembolism or cerebral microangiopathy were genotyped for 4 haplotype tagging SNPs (rs3093075, rs1205, rs1130864 and rs1800947) in the CRP gene which have been shown to influence CRP serum concentrations. Geographically matched controls were drawn from 2 prospective population-based studies, the Dortmund Health Study and the Study of Health in Pomerania. The genetic association between the SNPs and stroke was assessed using SNP and haplotype approaches. Results were adjusted for covariates by logistic regression. Results: All 4 CRP SNPs reside in one linkage disequilibrium block. None of the SNPs or SNP haplotypes were associated with ischemic stroke as a whole. Three SNPs (rs3093075, rs1130864 and rs1800947) showed a significant association with microangiopathic stroke. A common 4-SNP haplotype was protective while 2 rarer haplotypes conferred susceptibility to microangiopathic stroke. All associations remained significant after adjustment for sex, age, hypertension, diabetes mellitus and hypercholesterolemia and after correction for multiple testing using the ‘false discovery rate’ method. Conclusion: Genetic variation in the CRP gene is associated with microangiopathic but not macroangiopathic or cardioembolic stroke in a large German stroke sample.
Lipid Rafts, Pseudotyping, and Virus-Like Particles: Relevance of a Novel, Configurable, and Modular Antigen-Presenting Platform
Authors: Kueng Hans J. , Schmetterer Klaus G. , Pickl Winfried F.
Published: August 2010

Antigen presentation by professional antigen-presenting cells (APC) is the first step towards the initiation of an adaptive immune response carried out by naïve T lymphocytes. For this purpose, antigens are presented in the form of peptide/major histocompatibility complexes (pMHC) on APC to the antigen receptor of T cells. For sustained T cell activation to occur, numerous additional molecules specifically expressed on the surface of APC have to synergize with pMHC to stimulate a given T lymphocyte. Moreover, soluble factors such as cytokines critically contribute to the specific milieu during T cell activation. APC ‘talk’ to T cells only when they engage in intimate physical interaction. The cell biological correlate of this APC-T cell interaction is commonly referred to as the formation of an immunological synapse. In this review we aim to provide an overview of a novel cell-free antigen-presenting platform, i.e. virus-like particles (VLP) decorated with immune receptors of choice, which was devised to overcome the molecular and cell biological complexity of the APC side of the immunological synapse. In the past we have demonstrated that immune receptor-decorated VLP are able to activate, modulate, or abrogate antigen-specific T lymphocyte responses. Thus, antigen-specific VLP represent a valuable tool which might help to explore and understand the function of antigen-specific T lymphocytes in more detail and might thus open new avenues for the modulation of pathologic T lymphocyte responses, e.g. for the treatment of allergic diseases.
A Novel Function of Siglec-9 A391C Polymorphism on T Cell Receptor Signaling
Authors: Cheong Kyung Ah , Chang Yoon-Seok , Roh Joo Young , Kim Bum-Jun , Kim Myung-Nam , Park Youn Min , Park Hai Jin , Kim Nam-Doo , Lee Chang-Hoon , Lee Ai-Young
Published: August 2010

Background: Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are the best-characterized immunoglobulin-type lectins. There is a growing amount of data linking Siglec and autoimmune diseases. The recently identified Siglec-9 inhibits T cell receptor (TCR)-mediated signaling which has been demonstrated by site-directed mutagenesis. In human Siglec-9, at least 8 nonsynonymous SNPs have been detected without functional studies. This study examined the SNP(s) related to TCR-mediated signaling. Methods: Since the functions of Siglecs are modulated by their interaction with sialic-acid-containing carbohydrate groups, a molecular modeling analysis of carbohydrate binding interactions and an RBC binding analysis were performed using the 8 SNPs. The TCR-mediated signaling was analyzed with the downstream signaling molecules ZAP-70 and IL-2. Results: This study revealed that an A391C polymorphism is the only mutant related to the binding. Jurkat T cells transfected with the A391C mutant reduced the inhibition of ZAP-70 phosphorylation and IL-2 production compared to cells transfected with the wild type. Conclusions: Siglec-9 A391C was the only polymorphism related to TCR-mediated signaling in human Siglec-9, resulting in less inhibition compared to the wild type.
Ability of Pollen Cytoplasmic Granules to Induce Biased Allergic Responses in a Rat Model
Authors: Abou Chakra Oussama , Rogerieux Françoise , Poncet Pascal , Sutra Jean-Pierre , Peltre Gabriel , Sénéchal Hélène , Lacroix Ghislaine
Published: August 2010

Background: Grass pollen is one of the most important aeroallergens in Europe. It highly contributes to respiratory allergic diseases, mainly allergic rhinitis. In contact to water or airborne pollutants, pollen grains can release pollen cytoplasmic granules (PCGs) containing allergens. Because of their size (<5 µm), PCGs may penetrate deeper into the lungs to induce higher allergic responses, such as asthma. They have been associated with thunderstorm-related asthma. The aim of this study was to evaluate, with Brown Norway rats, the allergenic potential of isolated PCGs and to compare it with the allergenicity of whole timothy grass pollen. Methods: Rats were sensitized (day 0) and challenged (day 21), in controlled comparative conditions, with pollen grains (0.5 mg) or PCGs (4.5 × 107 and 0.5 mg). At day 25, blood samples, bronchoalveolar lavage fluid (BALF) and bronchial lymph node were collected. IgE and IgG1 levels in sera were assessed by ELISA. Alveolar cells, protein and cytokine concentrations were quantified in BALF. T cell proliferation, in response to pollen or granules, was performed by lymph node assay. Results: The results showed that proliferative responses of lymph node cells were similar in PCG- and pollen-sensitized rats. IgE and IgG1 levels were higher in pollen- than in PCG-sensitized rats. However, eosinophils, lymphocytes and pro-allergy cytokines in BALF were higher in PCG- than in pollen-sensitized rats. Conclusions: Thus, PCGs, able to deeply penetrate in the respiratory tract, induced local and strong allergic and inflammatory responses more linked with asthma- than rhinitis-related allergic symptoms.
Anti-Immunoglobulin E Treatment of Patients with Recalcitrant Physical Urticaria
Authors: Metz Martin , Altrichter Sabine , Ardelean Elena , Keβler Birgit , Krause Karoline , Magerl Markus , Siebenhaar Frank , Weller Karsten , Zuberbier Torsten , Maurer Marcus
Published: August 2010

In physical urticaria, exogenous physical factors such as thermal triggers, solar radiation and mechanic triggers including friction or pressure are responsible for the elicitation of symptoms in the skin of patients. Avoidance of the respective stimulus is usually difficult or impossible, and many patients are not sufficiently treated with standard antihistamines. We report that treatment with omalizumab (Xolair®) of 7 patients with physical urticarias [solar urticaria (n = 2), urticaria factitia/symptomatic dermographism (n = 2), cold urticaria, delayed pressure urticaria and localized heat urticaria] resulted in complete symptom control within days after the first injection in 5 patients. In 1 patient, symptoms improved after increasing the dose of omalizumab, and 1 patient with localized heat urticaria did not respond significantly to treatment. Before anti-immunoglobulin E treatment, all patients had suffered from their physical urticaria for years and had had numerous unsuccessful therapies. The overall excellent responses to omalizumab treatment reported here indicate that anti-immunoglobulin E is a safe and effective treatment for recalcitrant physical urticarias.
Immunomodulatory Effects of Macrolide Antibiotics – Part 1: Biological Mechanisms
Authors: Altenburg J. , de Graaff C.S. , van der Werf T.S. , Boersma W.G.
Published: August 2010

Macrolide antibiotics are well known for their antibacterial and anti-inflammatory properties. This article provides an overview of the biological mechanisms through which macrolides exert this ‘double effect’. Their antibacterial effect consists of the inhibition of bacterial protein synthesis, impaired bacterial biofilm synthesis, and the attenuation of other bacterial virulence factors. Apart from these direct antimicrobial effects, macrolides are known for their modulating effect on many components of the human immune system. By influencing the production of cytokines, they have a dampening effect on the proinflammatory response. Furthermore, the majority of cells involved in the immune response are, in one way or another, influenced when macrolide antibiotics are administered. Having such an obvious effect on the various aspects of the immune system, macrolides seem to be exceptionally suited for the treatment of chronic inflammatory diseases.
Immunomodulatory Effects of Macrolide Antibiotics – Part 2: Advantages and Disadvantages of Long-Term, Low-Dose Macrolide Therapy
Authors: Altenburg J. , de Graaff C.S. , van der Werf T.S. , Boersma W.G.
Published: August 2010

The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide treatment. Macrolide maintenance therapy has been proven to be of benefit in diffuse panbronchiolitis and CF, presumably due to an anti-inflammatory mechanism of action in addition to its direct antimicrobial effect. Solid evidence to justify this treatment regimen for non-CF bronchiectasis, asthma, or sinusitis is still lacking, although a beneficial effect of long-term macrolide therapy has been found in small clinical trials on these subjects. Data from randomized trials of long-term macrolide treatment in COPD are conflicting. A sufficiently long duration of treatment and the careful selection of patients appears to be crucial. Aside from its beneficial effects, possible side effects of macrolide treatment should be taken into account, the most important of these being gastrointestinal upset and cardiac arrhythmias. Development of macrolide resistance among respiratory pathogens is very common during long-term macrolide treatment. Whether this finding is clinically significant is a matter of debate.
Resource Utilization in Patients with Brain Metastases Managed with Best Supportive Care, Radiotherapy and/or Surgical Resection: A Markov Analysis
Authors: Nieder Carsten , Norum Jan , Stemland Jørn G. , Dalhaug Astrid
Published: August 2010

Objective: In spite of the large number of patients and increasing financial pressure on health care budgets worldwide, limited data on resource utilization after diagnosis of brain metastases are available. Methods: Prospective data were collected on all patients diagnosed with brain metastases during a time period of 2 years (n = 53). Treatment was best supportive care (BSC), primary radiotherapy (RT) and/or surgical resection. Eighty-five percent of patients had active extracranial disease. Costs were calculated from the hospital and nursing home’s point of view. Results: Overall, 11,532 patient days were analyzed. Treatment per patient amounted to 0.8 courses of whole-brain RT, 0.2 neurosurgical procedures, 0.1 radiosurgical procedures and 1.3 cycles of chemotherapy. Median survival in the BSC, RT and neurosurgery groups was 1.4, 4.6 and 11.0 months, respectively. Chemotherapy was associated with longer median survival. Four percent of the remaining lifetime was spent in nursing homes and 8% within hospitals. Forty-three percent of all hospital days and 47% of deaths were related to non-neurologic causes. The total cost per patient was 24,649 EUR (34,841 USD) and the corresponding cost per life year was 43,955 EUR (62,130 USD). Hospital care was the main cost factor. Conclusions: A considerable amount of resources is utilized in this patient group. Better tools for avoiding overtreatment and selecting patients for appropriate therapy are needed to achieve maximum value for money.
Autism and Perplexity: A Qualitative and Theoretical Study of Basic Subjective Experiences in Schizophrenia
Authors: Henriksen Mads G. , Škodlar Borut , Sass Louis A. , Parnas Josef
Published: August 2010

Background: Autistic traits and perplexity are considered core features of schizophrenia in phenomenological psychiatry. They express a fundamental disturbance of the self-world relation (including disturbances of self and intersubjectivity). The aim of our study was to examine this disturbance by exploring in detail how autism and perplexity are experienced subjectively. Methods: It is a qualitative single-case study. In order to fully examine our patient’s experiences within the context of his experiential world and not only as isolated or decontextualized symptoms, we applied a heideggerian framework, i.e. Heidegger’s exhaustive account of the self-world relation (care). Results: Through the framework of care, we discovered a profound disturbance of the self-world relation in our patient, characterized by subtle experiences of estrangement, anxiety and exposure. We found these experiences to be enduring, pervasive and generative for the development of other symptoms. Conclusions: We argue that these experiences can be seen as experiential correlates of schizotypy and of vulnerability to schizophrenia, and furthermore that an understanding of these experiences can play a role in diagnostic and differential diagnostic procedures, e.g. in early detection or in the search for high-risk individuals, as well as in the psychotherapy of schizophrenia.
Erythropoietin in Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Ott Ilka , Schulz Stefanie , Mehilli Julinda , Fichtner Stefanie , Hadamitzky Martin , Hoppe Katharina , Ibrahim Tareq , Martinoff Steffan , Massberg Steffen , Laugwitz Karl-Ludwig , Dirschinger Josef , Schwaiger Markus , Kastrati Adnan , Schömig Albert ,   for the REVIVAL-3 Study Investigators
Published: August 2010

Background—

Erythropoietin improves myocardial function in experimental models of myocardial infarction. The aim of the present study was to determine the value of erythropoietin in patients with acute ST-elevation myocardial infarction.

Methods and Results—

This randomized, double-blind study included 138 patients admitted with acute ST-elevation myocardial infarction and treated with primary percutaneous coronary intervention. Patients were randomly assigned to receive epoetin-β (3.33×104 U, n=68) or placebo (n=70) immediately and at 24 and 48 hours after percutaneous coronary intervention. The primary end point was left ventricular ejection fraction after 6 months measured by MRI. Other end points included infarct size at 5 days and 6 months. Clinical adverse events (death, recurrent myocardial infarction, stroke, and infarct-related artery revascularization) were investigated at 30 days and 6 months. Left ventricular ejection fraction at 6-month follow-up was 52.0±9.1% in the erythropoietin group compared with 51.8±9.3% in the placebo group (
P
=0.92). Five days after percutaneous coronary intervention, left ventricular ejection fraction was 49.4±8.0% in the erythropoietin group and 50.8±7.3% in the placebo group (
P
=0.32); infarct size was 26.8±20.9% and 28.3±24.4% (
P
=0.76) and decreased to 17.3±14.3% and 20.9±16.4% at 6-month follow-up (
P
=0.27). The cumulative 6-month incidence of death, recurrent myocardial infarction, stroke or target vessel revascularization was 13.2% in the erythropoietin group and 5.7% in the placebo group (hazard ratio, 2.36; 95% confidence interval, 0.73 to 7.66;
P
=0.15).

Conclusions—

In patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention, erythropoietin treatment did not improve left ventricular ejection fraction or reduce infarct size but may increase clinical adverse events.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00390832.
The Platelet Activity After Clopidogrel Termination (PACT) Study
Authors: Frelinger Andrew L. , Barnard Marc R. , Fox Marsha L. , Michelson Alan D.
Published: August 2010

Background—

“Rebound” platelet hyperreactivity after discontinuation of clopidogrel has been proposed to lead to increased thrombotic risk, including late stent thrombosis. However the hypothesis that discontinuation of clopidogrel results in platelet hyperreactivity has never been rigorously tested. We therefore performed a randomized, double-blind, placebo-controlled, crossover study: the Platelet Activity after Clopidogrel Termination (PACT) study.

Methods and Results—

Platelet reactivity in 15 healthy subjects was measured at baseline, during clopidogrel 75 mg or placebo daily for 14 days, and on days 1, 4, 8, 11, 15, and 45 after discontinuation of clopidogrel or placebo. Platelet reactivity was assessed by (1) platelet surface activated GPIIb-IIIa and surface P-selectin (by whole blood flow cytometry) in response to ADP 0.5, 1, and 20 μmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 μmol/L; and collagen/epinephrine 5 μg/mL/5 μmol/L, (2) light transmission aggregation with ADP 2.5, 5, and 20 μmol/L; TRAP 2 and 20 μmol/L; and collagen 6 μg/mL, (3) whole blood impedance aggregation with ADP 1.6 and 6.5 μmol/L; TRAP 4 and 32 μmol/L; and collagen 3.2 μg/mL, and (4) plasma soluble CD40 ligand (by ELISA). Immature platelet fraction was measured in the Sysmex XE-2100. At no time point after discontinuation of clopidogrel was platelet reactivity, as determined by any assay end point, or the immature platelet fraction significantly greater than after discontinuation of placebo.

Conclusions—

This randomized, double-blind, placebo-controlled, crossover study demonstrates that discontinuation of clopidogrel does not result in “rebound” platelet hyperreactivity, as determined by multiple time points, assays, agonists, and agonist concentrations.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00619073.
“Speaking a Mutual Language”: The Negro People's Theatre in Chicago
Authors: Barton Melissa
Published: August 2010

Putting black characters in their plays settled some formal debates for the Popular Front's new theatre, but it created entirely new questions about how the movement would involve actual African Americans. Fanny McConnell and Chicago's Negro People's Theatre (1938–1940) offered some answers.
Brown Punk: Kalup Linzy's Musical Anticipations
Authors: Nyong'o Tavia
Published: August 2010

How might a song carry the past without being burdened by history? In his performances for the camera, for audio recordings, and for live audiences, the artist Kalup Linzy explores the urgency of this question for contemporary black and queer subjects. Linzy's 2009 video song cycle, SweetBerry Sonnet, is a musical archive of radical passivity—one that manifests the anticipatory stance taken towards the world by the multiple personae Linzy invents for his live performances and videos.
Wooster Baroque
Authors: Jakovljevic Branislav
Published: August 2010

In the decade following 9/11, the Wooster Group staged three landmark 17th-century plays, Phaedra, Hamlet, and La Didone. This turn to baroque theatre is both a comment on American culture of the first decade of the 21st century and a significant departure in the history of the group itself.
Steve Paxton's “Interior Techniques”: Contact Improvisation and Political Power
Authors: Turner Robert
Published: August 2010

Steve Paxton's contact improvisation, though meant to develop our “habit of attending” to sensations and reflexes to overcome American democracy's conditioning in “voluntary slavery,” has instead mainly become an apolitical, “spiritual” practice. But CI could, by showing the relation between culture and conscious experience, radicalize participation in all our relations.
Driving Deeper into That Thing: The Humanity of Heiner Goebbels's Stifters Dinge
Authors: Bell Gelsey
Published: August 2010

Heiner Goebbels's music theatre work Stifters Dinge is a performance without human performers, a “no-man show” in which things are the thing. In its exhibition of mobile scenic elements and automated musical instruments, it is a meditation on objecthood, materality, and the environment that nevertheless reveals a humanity at its center.
King/Cate: Stardom, Aura, and the Stage Figure in the Sydney Theatre Company's Production of Richard II
Authors: McGillivray Glen
Published: August 2010

Spectatorship in the theatre is a complex business—particularly when a star is involved. So how does one separate the star from her aura and the actor from her role? When Cate Blanchett was cast as Richard II, her film-star aura concatenated with the mystery of kingly presence through the operation of the Stage Figure.