bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular Disease in the Metabolic Syndrome: Do We Need to Target the Microcirculation to Treat Large Vessel Disease?
Authors: Krentz Andrew J. , Clough Geraldine , Byrne Christopher D.
Published: July 2009

The metabolic syndrome of vascular risk is threatening large numbers of ever-younger people. To date, the syndrome has been chiefly viewed as a potential risk marker that confers a heightened probability of developing type 2 diabetes and occlusive atherothrombotic disease of large- and medium-sized arteries. Accumulating evidence suggests that the components of the metabolic syndrome may also adversely affect the microvasculature through several inter-related mechanisms. These include the following observations: classic risk factors for macrovascular disease such as high blood pressure and dyslipidaemia also accelerate microvascular complications of diabetes, lesser disturbances of glucose metabolism (i.e. impaired glucose tolerance) may be associated with some forms of microvascular dysfunction, non-glucose intermediary metabolites may promote renovascular hypertension thereby damaging the microvasculature, and insulin resistance appears to be directly associated with microvascular dysfunction. In turn, microvascular complications such as nephropathy and autonomic neuropathy may promote the development and progression of atherosclerosis. We argue that the vascular implications of the metabolic syndrome should be broadened to include the microvasculature. The hypothesis that vascular events can be prevented, or at least deferred, through earlier therapeutic intervention in pre-diabetic subjects with glucose intolerance is amenable to testing in clinical trials.
Micromanaging Vascular Biology: Tiny MicroRNAs Play Big Band
Authors: Sen Chandan K. , Gordillo Gayle M. , Khanna Savita , Roy Sashwati
Published: July 2009

Micro-RNAs (miRNAs) are estimated to regulate 30% of the human genome primarily through translational repression. In 2005–2008, the first series of observations establishing the key significance of miRNAs in the regulation of vascular biology came from experimental studies involved in arresting miRNA biogenesis to deplete the miRNA pools of vascular tissues and cells. Dicer-dependent biogenesis of miRNA is required for blood vessel development during embryogenesis and wound healing. miRNAs regulate redox signaling in endothelial cells, a key regulator of vascular cell biology. miRNAs that regulate angiogenesis include miRNA 17–5p, cluster 17–92, 21, 27a&b, 126, 130a, 210, 221, 222, 378 and the let7 family. miRNAs also represent a new therapeutic target for the treatment of proliferative vascular diseases as well as hypertension. Evidence supporting the regulation of inducible adhesion molecules by miRNA supports a role of miRNAs in regulating vascular inflammation. Productive strategies to safely up-regulate as well as down-regulate miRNAs in vivo are in place and being tested for their value in disease intervention. Prudent targeting of non-coding genes such as miRNAs, which in turn regulates large sets of coding genes, holds promise in gene therapy. Recent developments in miRNA biology offer lucrative opportunities to manage vascular health.
MT1-MMP-Mediated Cleavage of Decorin in Corneal Angiogenesis
Authors: Mimura Tatsuya , Han Kyu Yeon , Onguchi Tatsuya , Chang Jin-Hong , Kim Tae-im , Kojima Takashi , Zhou Zhongjun , Azar Dimitri T.
Published: July 2009

Background/Aims: Decorin has been shown to have antiangiogenic properties. In this study, we evaluate the involvement of membrane type 1-matrix metalloproteinase (MT1-MMP), a proangiogenic enzyme, in decorin cleavage in the cornea. Methods: MT1-MMP expression was confirmed immunohistochemically in keratocytes and immortalized corneal fibroblast cell lines. Corneal micropockets of bFGF were used to assess the expression of decorin and MT1-MMP. Western blotting was used to evaluate decorin degradation by MT1-MMP. Aortic ring tube formation assays were used to assay the inhibitory effect of decorin and stimulatory effect of MT1-MMP on vascular endothelial cells in vitro. Results: We show that MT1-MMP expression is upregulated following bFGF pellet implantation in the cornea in vivo, and that MT1-MMP cleaves decorin in a time- and concentration-dependent manner in vitro. Furthermore, the addition of MT1-MMP reduces the inhibitory effects of decorin on aortic ring tube formation in vitro. Cleavage of decorin by MT1-MMP-deficient corneal cell lysates is diminished relative to that by wild-type corneal cell lysates, and an MT1-MMP knockin restores decorin processing in vitro. Conclusion: The proangiogenic role of MT1-MMP in the cornea may be mediated, in part, by facilitated cleavage of corneal decorin.
Differential Expression of Pancreatitis-Associated Protein and Thrombospondins in Arterial versus Venous Tissues
Authors: Szasz Theodora , Eddy Susan , Paulauskis Joseph , Burnett Robert , Ellekilde Merete , Iovanna Juan L. , Watts Stephanie W.
Published: July 2009

Background/Aims: Arteries and veins modulate cardiovascular homeostasis and contribute to hypertension pathogenesis. Functional differences between arteries and veins are based upon differences in gene expression. To better characterize these expression patterns, and to identify candidate genes that could be manipulated selectively in the venous system, we performed whole genome expression profiling of arteries and veins. Methods: We used the CodeLink platform and the major artery (thoracic aorta) and vein (caudal vena cava) of the rat. Results: The most prominent difference was pancreatitis-associated protein (PAP1), expressed 64-fold higher in vena cava versus aorta. Expression of mRNA for thrombospondins (TSP-1, TSP-4) was greater than 5-fold higher in veins versus arteries. Higher mRNA expression of TSP-1, TSP-2, TSP-4 and PAP1 in vena cava versus aorta was confirmed by PCR. Immunohistochemical analysis of tissue sections qualitatively confirmed a higher expression of these proteins in vena cava versus aorta. Conclusion: This is the first gene array study of adult rat arterial and venous tissues, and also the first study to report differences in inflammatory genes between arteries and veins. Data from these studies may provide novel insights into the genetic basis for functional differences between arteries and veins in health and disease.
Effects of Pathological Flow on Pulmonary Artery Endothelial Production of Vasoactive Mediators and Growth Factors
Authors: Li Min , Stenmark Kurt R. , Shandas Robin , Tan Wei
Published: July 2009

Background: Alterations in pulmonary blood flow are often associated with the initiation and progression of pulmonary vascular disease. However, the cellular mechanisms involved in mediating flow effects in the pulmonary circulation remain unclear. Depending on the disease condition, flow may be extremely low or high. We therefore examined effects of pathologically low and high flow on endothelial production of factors capable of affecting pulmonary vascular tone and structure as well as on potential underlying mechanisms. Methods: Flow effects on pulmonary endothelial release of NO, PGF1a, ET-1 and TxB2, on expression of total and phosphorylated eNOS as well as Akt, and on VEGF were examined. Additionally, in a coculture system, effects of flow-exposed endothelial cells on smooth muscle (SM) proliferation and contractile protein were studied. Results: Compared to physiological flow, pathologically high and low flow attenuated endothelial release of NO and PGF1a, and enhanced release of ET-1. Physiological flow activated the Akt/eNOS pathway, while pathological flow depressed it. Pathologically high flow altered VE-cadherin expression. Pathologically high flow on the endothelium upregulated α-SM-actin and SM-MHC without affecting SM proliferation. Conclusion: Physiological flow leads to production of mediators which favor vasodilation. Pathological flow alters the balance of mediator production which favors vasoconstriction.
Myeloid Lineage of Human Endothelial Outgrowth Cells Circulating in Blood and Vasculogenic Endothelial-Like Cells in the Diseased Vessel Wall
Authors: Liu Chunsheng , Wang Shaohua , Metharom Pat , Caplice Noel M.
Published: July 2009

Endothelial injury is a major step in the pathogenesis of atherosclerosis. Accumulated data suggest endothelial progenitor cells can derive from various sources, including the host bone marrow, circulating blood mononuclear cells, as well as resident precursors within the vessel wall. Early experimental animal data supported a haematopoietic origin for vascular precursors, but more recently cells of myeloid lineage have been suggested as precursors of endothelial and smooth muscle cells. However, to date, little evidence exists to support a myeloid lineage-endothelial cell differentiation pathway within the vasculature of human subjects. Here, we undertook two sets of experiments aimed at determining whether (a) blood endothelial outgrowth cells (EOC) had a myeloid lineage and whether (b) chimeric endothelial-like cells within the neovasculature of gender-mismatched cardiac transplant arteriopathy subjects shared common myelomonocytic markers. We show here that in vitro blood-derived EOC and recipient-derived endothelial-like cells participating in vasculogenesis in vivo share some myeloid immunophenotypes. Additionally, these microvascular chimeric cells show no evidence of tetraploidy or cell fusion.
Adjusting Flow-Mediated Dilation for Shear Stress Stimulus Allows Demonstration of Endothelial Dysfunction in a Population with Moderate Cardiovascular Risk
Authors: Padilla Jaume , Johnson Blair D. , Newcomer Sean C. , Wilhite Daniel P. , Mickleborough Timothy D. , Fly Alyce D. , Mather Kieren J. , Wallace Janet P.
Published: July 2009

Background/Aims: Although normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress (FMD:shear stress ratio) has been proposed to improve this measure of endothelial function, the clinical utility of FMD normalization has not yet been demonstrated. We tested (1) whether following conventional 5-min forearm occlusion, the FMD:shear stress ratio would discriminate a population with moderate cardiovascular risk (MR) from a low-risk (LR) population, and (2) whether the dose-response profile relating shear stress to FMD would be different between the 2 populations. Methods: Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 MR and 20 LR subjects by manipulating forearm cuff occlusion duration. Brachial artery diameters and velocities were measured via high-resolution ultrasound. To quantify the hyperemic stimulus, shear stress area under the curve was individually calculated for the duration of time-to-peak dilation. Results: Following 5-min of forearm occlusion, FMD:shear stress ratio (p = 0.041), but not FMD (p = 0.286), discriminated MR from LR. The slope of the shear stress-FMD regression line was lower in MR compared to the LR (p <0.001). Conclusion: The FMD:shear stress ratio distinguished reduced endothelial function in a population with MR. The dose-response profile of the shear stress-FMD relationship appears to differ between populations of distinct cardiovascular risk.
Leptin Stimulated C-Reactive Protein Production by Human Coronary Artery Endothelial Cells
Authors: De Rosa Salvatore , Cirillo Plinio , Pacileo Mario , Di Palma Vito , Paglia Antonella , Chiariello Massimo
Published: July 2009

Background: Obesity and cardiovascular disease are closely related. Leptin, an adipocyte-produced hormone, is associated with increased cardiovascular risk. Increased plasma levels of leptin are measurable in the plasma of obese individuals. However, the possible links between obesity and cardiovascular disease are not completely understood. C-reactive protein (CRP) is a predictor of future cardiovascular events and plays a role in atherothrombotic disease. Thus, we evaluated whether leptin might play a role in cardiovascular disease, investigating its effects on CRP production by human coronary artery endothelial cells in culture. Methods and Results: Leptin induced CRP mRNA transcription as demonstrated by semiquantitative and real-time polymerase chain reaction as well as the release of CRP in the culture medium in a concentration-dependent fashion. Leptin-induced production of CRP was mediated through the RhoA activation of protein kinase Cβ since both protein kinase C and RhoA pathway inhibitors prevented these leptin effects. Lovastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, by modulating the RhoA activation, significantly reduced leptin-induced CRP production. Conclusions: This study describes the close relationship between leptin and CRP, providing support to the view that this adipokine, besides being involved in the pathophysiology of obesity, might play a relevant role as an active partaker in obesity, inflammation and atherothrombosis.
Common Variable Immunodeficiency: Etiological and Treatment Issues
Authors: Deane Sean , Selmi Carlo , Naguwa Stanley M. , Teuber Suzanne S. , Gershwin M. Eric
Published: July 2009

One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients.
Extensive IgE Cross-Reactivity towards the Pooideae Grasses Substantiated for a Large Number of Grass-Pollen-Sensitized Subjects
Authors: Johansen Niels , Weber Richard W. , Ipsen Henrik , Barber Domingo , Broge Louise , Hejl Charlotte
Published: July 2009

Background: Allergy to taxonomically related species is a common phenomenon caused by the same immunological receptor cross-reacting to homologous allergens from different species. Knowledge of patterns of cross-reactivity is crucial for the selection of optimal products for diagnosis and for specific immunotherapy. The objective of this study was to investigate patterns of serum IgE cross-reactivity towards pollens from various grass species. Methods: With grass group 1 allergens as the representative group, amino acid sequence alignment, structural modelling and comparison of 3D surface characteristics were performed to exemplify the molecular basis of IgE cross-reactivity. IgE binding to extracts from ten different grass species was determined (total number of data pairs >19,000), and IgE inhibition experiments using Phleum pratense were performed. Results: Analysis of surface topography for group 1 grass allergens demonstrated ample space for IgE binding epitopes in surface areas conserved among Pooideae grasses. Significant correlation was observed between the serum IgE response to P. pratense extract and extracts from the other Pooideae grasses analyzed. P. pratense extract was demonstrated to inhibit the binding of IgE to the allergens in all of the extracts included in the investigation, indicating patient IgE to be primarily directed towards common epitopes. Conclusion: Extensive IgE cross-reactivity was observed towards the allergens of the Pooideae grasses, meaning that the immune system does not appear to distinguish based on the IgE level between the different species of this subfamily. The data suggest equal effect upon use of any of the Pooideae species for diagnostic as well as therapeutic purposes.
Procaterol Potentiates the Anti-Inflammatory Activity of Budesonide on Eosinophil Adhesion to Lung Fibroblasts
Authors: Yoshida Norihiro , Muraguchi Masahiro , Kamata Masayuki , Ikezono Katsumi , Mori Toyoki
Published: July 2009

Background: The interaction between leukocytes and various parenchymal cells is the first step of inflammation. Therefore, the adhesion of eosinophils to lung fibroblasts is thought to be a crucial step in the inflammatory process of asthma. Procaterol, a β2-selective full agonist, is currently prescribed for patients with asthma. In addition to its potent bronchodilatory action, the agonist has been reported to have anti-inflammatory actions. In this study, to examine whether procaterol can potentiate the anti-inflammatory action of glucocorticoids, the effect of procaterol on eosinophil adhesion to normal human lung fibroblasts (NHLF) was assessed in the presence and absence of budesonide, one of the most potent glucocorticoids. Methods: Following pretreatment of NHLF with tumor necrosis factor-α (TNF-α) in the presence of various concentrations of procaterol and/or budesonide, the eotaxin-stimulated eosinophil adhesion was determined using the peroxidase activity of eosinophils. To investigate the mechanism of the inhibitory action of procaterol, TNF-α-induced expression of adhesion molecules, ICAM-1 and VCAM-1, in NHLF was also evaluated. Results: Pretreatment with procaterol inhibited the adhesion of eosinophils to NHLF in a concentration-dependent manner, and shifted the concentration-response curve of budesonide to the left. Both procaterol and budesonide resulted in concentration-dependent inhibition of expression of ICAM-1 and VCAM-1 in NHLF, and an additive inhibitory effect was found when the agents were combined. Conclusions: Given the results of this study which indicated that procaterol exerted an additive action on the anti-inflammatory effect of budesonide, procaterol and glucocorticoids may provide better control for asthma when used together than when used separately.
Three-Year Follow-Up Study of Allergen-Induced in vitro Cytokine and Signalling Lymphocytic Activation Molecule mRNA Responses in Peripheral Blood Mononuclear Cells of Allergic Rhinitis Patients Undergoing Specific Immunotherapy
Authors: Nieminen K. , Laaksonen K. , Savolainen J.
Published: July 2009

Background: Allergen-specific immunotherapy (SIT) is known to affect the allergen-specific T helper cell (Th2/Th1) balance and to induce T regulatory (Treg) cells. These observations have usually been made during the first treatment year and often without symptom monitoring. This study was performed to investigate allergen-induced Th2 (IL-4, IL-5)-, Th1 [IFN-γ, IL-18, signalling lymphocytic activation molecule (SLAM)]- and Treg (IL-10)-type immune responses in peripheral blood mononuclear cells (PBMC) and their association with symptom improvement in allergic rhinitis patients after 3 years of SIT. Methods: Twenty patients were treated with SIT and 8 patients were studied as untreated controls. PBMC were collected before and after 1 and 3 years of SIT and stimulated with specific allergen. Cytokine and SLAM mRNA expression was determined by TaqMan® RT-PCR. Symptoms were recorded yearly using visual analogue scale (VAS) scoring. Results: IL-18, SLAM and IL-10 mRNA expression increased after 3 years of SIT, with a peak at 1 year, whereas IL-5 mRNA expression transiently decreased and IFN-γ mRNA expression transiently increased after 1 year of SIT. The increases in IL-18 and SLAM expression were not associated with symptom improvement, whereas decreases in both IL-4 expression and the IL-4/IFN-γ ratio after 1 year of SIT were found in patients with a good therapeutic outcome (>40 percentage unit reduction in VAS). Conclusions: SIT has long-term effects on allergen-specific immune responses. The induced Treg- and Th1-type responses persist over 3 years of SIT, whereas Th2-type responses are transiently decreased only during early therapy.
Evaluation of Receptor Expression on Immune System Cells in the Peripheral Blood of Asthmatic Children Undergoing Food Challenges
Authors: Krogulska Aneta , Wąsowska-Królikowska Krystyna , Polakowska Ewa , Chrul Slawomir
Published: July 2009

Background: The role of food allergens in the induction of allergic reactions in the airways is not completely understood. The aim of the present study was to evaluate fluorocytometric assays of the peripheral blood during food challenge tests in children with asthma and food allergy. Patients and Methods: 22 children with asthma and concomitant food allergy and 18 children with asthma without food allergy participated in the study. Oral challenge tests were performed using double-blind, placebo-controlled food challenge. Blood samples were collected before and 4 and 24 h after the challenge. CD25 and CD23 antigen expression was determined with monoclonal antibodies using a FACSCalibur flow. Results: The evaluation of the CD25+ T subpopulation and CD19+CD23+ B lymphocytes revealed statistically significant differences between the study group and the control group. In children with asthma and food allergy, the cell pool consisted (on average) of 9 ± 2.8% of CD3+CD25+ cells before the challenge and of 10.3 ± 3.8% (mean delta: 1.623; p = 0.01) after the provocation. However, placebo challenge did not significantly change the number of this T-lymphocyte subpopulation (mean delta: –0.121; p > 0.05). The highest increase in the CD25+ T-subpopulation expression was found in patients with respiratory reactions during the positive food challenge (mean delta: 4.065; p < 0.004). Conclusions: An increase in CD25+ T-lymphocyte and CD23 B-lymphocyte populations after food allergen challenge may indicate their significant role in the pathogenesis of the active phase of the immunoinflammatory process in children with asthma and concomitant food allergy.
Decreased Sputum Mature Dendritic Cells in Healthy Smokers and Patients with Chronic Obstructive Pulmonary Disease
Authors: Tsoumakidou Maria , Bouloukaki Izolde , Koutala Heleni , Kouvidi Katerina , Mitrouska Ioanna , Zakynthinos Spyros , Tzanakis Nikolaos , Jeffery Peter K. , Siafakas Nikolaos M.
Published: July 2009

Background: Asthmatics who smoke have decreased pulmonary mature dendritic cells (DCs). Chronic obstructive pulmonary disease (COPD) patients have an increased amount of pulmonary immature DCs. We hypothesized that healthy smokers and patients with COPD have decreased pulmonary mature DCs. Methods: We identified sputum DCs expressing the maturation markers CD83 and DC-lysosome associated membrane protein (DC-LAMP) and DC subpopulations (i.e. myeloid and plasmacytoid DCs) by flow cytometry in healthy smokers before they entered a smoking cessation trial (n = 30), in the same smokers after 6 months of smoking cessation (n = 11) and in COPD patients (n = 28, 14 current and 14 ex-smokers). 12 healthy never-smokers served as controls. DC numbers were expressed as percentage of total sputum CD45+ leukocytes. Results: CD83+ and DC-LAMP+ mature DCs were decreased in healthy smokers before they ceased smoking compared to after (p = 0.003 and p = 0.049, respectively) and in smokers before smoking cessation compared to never-smokers (p = 0.027 and p = 0.028, respectively). COPD patients, both current and ex-smokers, showed decreased CD83+ mature DCs compared to never-smokers and smokers after cessation (p = 0.042 and p = 0.004, respectively). Conclusions: Cigarette smoking and COPD per se are associated with a decrease in pulmonary mature DCs. We speculate that this reduction is involved in the immunopathogenesis of smoking-related respiratory disorders, such as COPD.
The Effect of Ultrasound Dissection in Thyroid Surgery
Authors: Witzel K. , von Rahden B.H.A. , Stein H.J.
Published: July 2009

Background: One of the most important aspects of thyroid surgery is hemostasis. The ultrasonically activated scalpel is described as a very useful instrument in thyroid surgery for the dissection and sealing of vessels. Our study compares the short-term results of endocrine surgery, with and without the use of ultrasonic devices. Methods: In a prospectively randomized trial, 96 patients with endemic goiter were operated by the same surgeon, one study group (n = 54 patients) being operated with the ultrasonic scalpel as an additional instrument. We measured the operating time, the number of ligatures needed as well as intraoperative and postoperative bleeding as surrogate markers for improvement of the surgical technique. Results: The ultrasound dissection technique significantly reduces surgery time (p = 0.048; ultrasound procedure average 68 min, conventional procedure average 83 min), intraoperative bleeding (p = 0.028) and the number of ligatures (p = 0.008; ultrasound procedure average 8.2, conventional procedure average 26.4). Conclusions: The use of an ultrasonically activated scalpel significantly improves bleeding control during thyroid resections and may also be beneficial with respect to cost reduction. Clinical application and further studies to characterize its role are justified.
A Simple Nonmydriatic Self-Retinal Imaging Procedure Using a Kowa Genesis-D Hand-Held Digital Fundus Camera
Authors: Ozerdem Ugur
Published: July 2009

Research on vascular adaptation to microgravity in the central nervous system requires a simple, noninvasive, direct imaging technique that can be performed with compact equipment. In this report we describe a practical, nonmydriatic, retinal self-imaging technique using a Kowa Genesis-D hand-held digital camera and a Black and Decker laser level. This simple technique will be useful to clinical physiologists conducting microgravity research, as well as for the studies of high-altitude medicine and aviation physiology.
Cochlear Reimplantation after Surgery for Electric-Acoustic Stimulation
Authors: Helbig Silke , Helbig Matthias , Rader Tobias , Mack Martin , Baumann Uwe
Published: July 2009

Background/Aims: Combined electric-acoustic stimulation (EAS) of the auditory system usually results in better speech understanding than electric stimulation only, assuming low-frequency hearing can be preserved. Treatment options and outcomes for 4 subjects experiencing compromised hearing after EAS surgery are discussed. Methods: Each subject underwent revision surgery to replace the original 21-mm electrode arrays used in EAS surgery with cochlear implants (CIs) with 31-mm arrays. Our aims were: (1) to investigate whether deeper insertion is possible, and (2) to evaluate the influence of electrode insertion angle by comparing speech perception scores before and after revision surgery. Results: Deeper insertion was feasible in all subjects. Speech understanding scores after reimplantation were comparable to those seen after the first intervention. Conclusion: A 360-degree insertion under EAS conditions provides sufficient speech understanding, even in cases of additional hearing loss. Reimplantation with a longer electrode array is feasible in former EAS patients.
Relationship between Psychosocial Factors and Onset of Multiple Sclerosis
Authors: Liu X.J. , Ye H.X. , Li W.P. , Dai R. , Chen D. , Jin M.
Published: July 2009

Objective: The aim of this study was to investigate the influence of psychosocial variables on patients with multiple sclerosis (MS) and the relationship between these variables and the onset of MS. Background: The current evidence indicates that many types of psychosocial factors are involved in the development and relapse of MS, and it has been suggested that they could serve as predictors as well. So far, little has been reported on the effect of psychosocial factors on MS and the relationship between psychosocial factors and the onset of MS. Methods: Forty-one patients, 15 males and 26 females, average age 37.44 ± 12.24 years (mean ± SD), were evaluated by the Life Event Scale, Eysenck Personality Questionnaire, Social Support Revaluate Scale and Symptom Check List 90 and compared with 41 equivalent healthy control subjects, 15 males and 26 females, average age 36.38 ± 12.84 years (mean ± SD). Disease, demographic, psychosocial and lifestyle factors were measured at baseline. Patients with MS were first diagnosed by 3 neurologists according to the Poser (1983) MS diagnostic criteria. Results: Significant differences were found between the MS and the control group in their negative emotions and symptoms such as depression, anxiety, obsession, phobia, tense interpersonal relationship and somatization disorder. Significant differences were found between the two groups in the total number of negative life events, their family problems and the utilization of social support. The scores for various negative emotions in the MS group correlated positively with those for neuroticisms in personality type, and negatively with those for introverted and extroverted personality. Many kinds of negative emotions in the MS group correlated positively with the total number of life events, negative life events and family problems. Many kinds of negative emotions in the MS group correlated negatively with the utilization of social support. Conclusion: The psychosocial factors are closely associated with MS onset and may play important roles in the development of the disease.
Risk Factors for Neurological Deficiency One Year after Blunt-Induced Traumatic Cervical Fracture
Authors: Pull ter Gunne Albert F. , Aquarius Annelies E. , Roukema Jan-Anne
Published: July 2009

Background/Aims: Little is known about the risk factors of neurological deficiency after blunt cervical fracture. This study was performed to identify factors predicting neurological deficiency after blunt cervical fracture. Methods: Within our Level I Trauma Center, we performed a retrospective case-control study. Patients with a cervical fracture after blunt trauma between January 2000 and December 2005 were identified. In total, 76 patients sustained a cervical fracture and survived 1 year after trauma. All patient files were reviewed. Patient and trauma characteristics were registered in an electronic database. Results: 26 patients were referred to the Neurology Department. Of these, 14 patients had complaints of sensory or motor loss and 12 patients were seen for sensory and motor loss. Involvement of the seventh cervical vertebrae (p = 0.030) and spinal cord compression were found to be independent significant risk factors for sensory or motor loss. The injury severity score (p = 0.001) and involvement of the vertebral body (p = 0.042) were significantly associated with sensory and motor loss. Conclusion: During patient evaluation, the identified variables should be taken into account. If one understands the risk factors, then it is possible to explain the expected outcome after the spine fracture.
Posterior Reversible Encephalopathy Syndrome: Is There a Difference between Pregnant and Non-Pregnant Patients?
Authors: Roth C. , Ferbert A.
Published: July 2009

Background: Clinical and imaging abnormalities similar to those seen in posterior reversible encephalopathy syndrome (PRES) have been observed in patients with eclampsia. It remains unclear whether both conditions are in fact the same disease entity. Methods: We retrospectively identified 21 patients with PRES and separated them into 2 groups: patients who were symptomatic during pregnancy, and a group of non-pregnant patients. We recorded symptoms, premedical history and paraclinical investigations of both groups and compared them to each other. Results: We found 8 pregnant patients and 13 non-pregnant patients with PRES. There was no difference between both groups with regard to symptoms, cerebral imaging, or outcome, apart from a difference in age, the premedical history and a significantly higher occurrence of headache in the pregnant group. All of our pregnant women were primigravid. Follow-up was done over a mean period of 2,171 (range 59–9,396) days. Overall, there was a good clinical outcome. Conclusion: We suggest that PRES in non-pregnant patients and eclampsia presenting with MRI abnormalities similar to those seen in PRES represent the same disease entity, but are triggered by different pathologies.
Diastolic Wall Shear Stress in the Internal Carotid Artery Is Associated with Different Cardiovascular Risk Factors than Systolic Wall Shear Stress
Authors: Palm-Meinders Inge H. , Box Frieke M.A. , de Craen Anton J.M. , Blauw Gerard J. , van Buchem Mark A. , van der Grond Jeroen
Published: July 2009

Background and Purpose: Wall shear stress (WSS) is the frictional force exerted by the circulating blood on the endothelium. Low systolic WSS is identified as an atherosclerotic risk factor. Recently, also the importance of diastolic WSS has been described. Still, it is unknown whether diastolic WSS carries similar cardiovascular risk factors compared to systolic WSS. Methods: Of 379 subjects (70–82 years, 56% male) diastolic and systolic WSS in the internal carotid arteries was determined. Results: After adjustment for age and gender, diastolic blood pressure was associated with systolic WSS (p = 0.02). Body mass index was associated with diastolic WSS (p = 0.04). Smoking was associated with diastolic WSS (p = 0.05). Myocardial infarction was associated with both systolic WSS (p = 0.04) and diastolic WSS (p < 0.01). No associations between cholesterol, HDL, LDL, triglycerides, history of diabetes, hypertension, angina pectoris, claudication, stroke, or any vascular disease were found with systolic or diastolic WSS. Conclusions: Our data indicates different cardiovascular risk factors for diastolic WSS compared to systolic WSS.
Osteoporosis after Stroke: A Review of the Causes and Potential Treatments
Authors: Carda Stefano , Cisari Carlo , Invernizzi Marco , Bevilacqua Maurizio
Published: July 2009

Osteoporosis is a known consequence of stroke, associated with an increased incidence of fractures, mainly of the hip, leading to further disability. The pattern of bone loss seen in stroke patients is different from that usually encountered with postmenopausal osteoporosis, since it is limited to the paretic side and more evident in the upper extremities. Several factors appear to have an influence on bone mass in stroke patients, such as the degree of paresis, gait disability and the duration of immobilization. The pathogenesis of osteoporosis after stroke remains unclear. Paresis, reduced mobility and reduced bone load seem to play a major role. Other factors such as nutritional and iatrogenic ones may also play an important part. In this paper, the clinical evidence, pathophysiology and possible treatments of poststroke osteoporosis will be reviewed.
Miller Fisher Syndrome: 10 Years’ Experience in a Third-Level Center
Authors: San-Juan O. Daniel , Martínez-Herrera José Fabián , Moreno García Jael , Fernández Gonzalez-Aragon Maricarmen , Del Castillo-Calcáneo Juan de Dios , Pérez-Neri Iván
Published: July 2009

Introduction: There are few studies regarding the clinical characteristics of Miller Fisher syndrome (MFS) in the Latin-American population. Methods: A retrospective analysis was made of the clinical characteristics, neurophysiology, treatment and prognosis of MFS patients between 1995 and 2005. Results: Nineteen MFS cases were documented, 12 of which did not receive immunosuppressive therapy. In both groups, the mean age was 36 years, 84% were male; onset in spring and fall was also predominant (73%), and antecedents of respiratory disease were found (79%). The mean duration of infectious symptoms was 7 days (1–11 days), and the mean interval between the onset of the infection and neurological symptoms was 7 days (1–30 days). The principal sign of onset was diplopia (63%). The mean delay between the onset of neurological symptoms and the beginning of recovery from ataxia, ophthalmoplegia and areflexia was 10 (1–30 days), 11 (1–30 days) and 14 (4–45 days) days, respectively, and the mean delay of the disappearance of ataxia, ophthalmoplegia and areflexia was 35 (10–121 days), 93 (18–244 days) and 64 (10–650 days) days, respectively. There was no significant difference between the group that received immunosuppression and the one that did not. Discussion: The natural course of MSF is characterized by excellent recovery; there were no differences between the two groups.
Evaluating Quality in Clinical Cancer Research: The M.D. Anderson Cancer Center Experience
Authors: Cox James D. , Giralt Sergio A. , Veazie Mary L. , Ajani Jaffer A. , Bruner Janet M. , Chan Ka Wah , Hittelman Walter N. , Hunt Kelly K. , Iyer Revathy B. , Karp Daniel D. , Kuban Deborah A. , Lippman Scott M. , Raad Issam I. , Rodriguez-Bigas Miguel A. , Zwelling Leonard A. , Markman Maurie
Published: July 2009

Background: Despite the unquestionable importance of clinically oriented research designed to test the safety and efficacy of new therapies in patients with malignant disease, there is limited information regarding strategies to evaluate the quality of such efforts at academic institutions. Methods: To address this issue, a committee of senior faculty at the University of Texas M.D. Anderson Cancer Center established specific criteria by which investigators from all departments engaged in clinical research could be formally evaluated. Scoring criteria were established and revised based on the results of a pilot study. Beginning in January 2004, the committee evaluated all faculty involved in clinical research within 35 departments. Scores for individual faculty members were assigned on a scale of 1 (outstanding) to 5; a score of 3 was set as the standard for the institution. Each department also received a score. The results of the evaluation were shared with departmental chairs and the Chief Academic Officer. Results: 392 faculty were evaluated. The median score was 3. Full professors more frequently received a score of 1, but all faculty ranks received scores of 4 and 5. As a group, tenure/tenure track faculty achieved superior scores compared to nontenure track faculty. Conclusions: Based on our experience, we believe it is possible to conduct a rigorous consensus-based evaluation of the quality of clinical cancer research being conducted at an academic medical center. It is reasonable to suggest such evaluations can be used as a management tool and may lead to higher-quality clinical research.
fMRI Activation during Observation of Others' Reach Errors
Authors: Malfait Nicole , Valyear Kenneth F. , Culham Jody C. , Anton Jean-Luc , Brown Liana E. , Gribble Paul L.
Published: July 2009

When exposed to novel dynamical conditions (e.g., externally imposed forces), neurologically intact subjects easily adjust motor commands on the basis of their own reaching errors. Subjects can also benefit from visual observation of others' kinematic errors. Here, using fMRI, we scanned subjects watching movies depicting another person learning to reach in a novel dynamic environment created by a robotic device. Passive observation of reaching movements (whether or not they were perturbed by the robot) was associated with increased activation in fronto-parietal regions that are normally recruited in active reaching. We found significant clusters in parieto-occipital cortex, intraparietal sulcus, as well as in dorsal premotor cortex. Moreover, it appeared that part of the network that has been shown to be engaged in processing self-generated reach error is also involved in observing reach errors committed by others. Specifically, activity in left intraparietal sulcus and left dorsal premotor cortex, as well as in right cerebellar cortex, was modulated by the amplitude of observed kinematic errors.
Patterns of Brain Activity Supporting Autobiographical Memory, Prospection, and Theory of Mind, and Their Relationship to the Default Mode Network
Authors: Spreng R. Nathan , Grady Cheryl L.
Published: July 2009

The ability to rise above the present environment and reflect upon the past, the future, and the minds of others is a fundamentally defining human feature. It has been proposed that these three self-referential processes involve a highly interconnected core set of brain structures known as the default mode network (DMN). The DMN appears to be active when individuals are engaged in stimulus-independent thought. This network is a likely candidate for supporting multiple processes, but this idea has not been tested directly. We used fMRI to examine brain activity during autobiographical remembering, prospection, and theory-of-mind reasoning. Using multivariate analyses, we found a common pattern of neural activation underlying all three processes in the DMN. In addition, autobiographical remembering and prospection engaged midline DMN structures to a greater degree and theory-of-mind reasoning engaged lateral DMN areas. A functional connectivity analysis revealed that activity of a critical node in the DMN, medial prefrontal cortex, was correlated with activity in other regions in the DMN during all three tasks. We conclude that the DMN supports common aspects of these cognitive behaviors involved in simulating an internalized experience.
Syntactic Unification Operations Are Reflected in Oscillatory Dynamics during On-line Sentence Comprehension
Authors: Bastiaansen Marcel , Magyari Lilla , Hagoort Peter
Published: July 2009

There is growing evidence suggesting that synchronization changes in the oscillatory neuronal dynamics in the EEG or MEG reflect the transient coupling and uncoupling of functional networks related to different aspects of language comprehension. In this work, we examine how sentence-level syntactic unification operations are reflected in the oscillatory dynamics of the MEG. Participants read sentences that were either correct, contained a word category violation, or were constituted of random word sequences devoid of syntactic structure. A time–frequency analysis of MEG power changes revealed three types of effects. The first type of effect was related to the detection of a (word category) violation in a syntactically structured sentence, and was found in the alpha and gamma frequency bands. A second type of effect was maximally sensitive to the syntactic manipulations: A linear increase in beta power across the sentence was present for correct sentences, was disrupted upon the occurrence of a word category violation, and was absent in syntactically unstructured random word sequences. We therefore relate this effect to syntactic unification operations. Thirdly, we observed a linear increase in theta power across the sentence for all syntactically structured sentences. The effects are tentatively related to the building of a working memory trace of the linguistic input. In conclusion, the data seem to suggest that syntactic unification is reflected by neuronal synchronization in the lower-beta frequency band.
Momentary Fluctuations in Allocation of Attention: Cross-modal Effects of Visual Task Load on Auditory Discrimination
Authors: Haroush Keren , Hochstein Shaul , Deouell Leon Y.
Published: July 2009

Even when our attention is dedicated to an important task, background processes monitor the environment for significant events. The mismatch negativity (MMN) event-related potential is thought to reflect such a monitoring process. Nevertheless, there is continuing debate concerning the susceptibility of the MMN to attentional manipulation. We investigated the trial-by-trial relationship between brain activity related to change detection, reflected in the MMN, and visual psychophysical performance—while varying task difficulty. We find that auditory change detection is indeed “automatic” in that MMN remains robust despite increasing (visual) task load. However, the MMN amplitude and latency are susceptible to both visual load and to momentary attentional fluctuations as reflected in success or failure to identify a following visual target. We conclude that background central auditory processing is sensitive to the demands of a visual task, and fluctuates based on moment-to-moment allocation of attentional resources to the visual task.
The Involvement of Occipital Cortex in the Early Blind in Auditory and Tactile Duration Discrimination Tasks
Authors: Van der Lubbe Rob H. J. , Van Mierlo Christa M. , Postma Albert
Published: July 2009

Early blind participants outperform controls on several spatially oriented perceptual tasks such as sound localization and tactile orientation discrimination. Previous studies have suggested that the recruitment of occipital cortex in the blind is responsible for this improvement. For example, electroencephalographic studies showed an enlarged posterior negativity for the blind in these tasks compared to controls. In our study, the question was raised whether the early blind are also better at tasks in which the duration of auditory and tactile stimuli must be discriminated. The answer was affirmative. Our electroencephalographic data revealed an enlarged posterior negativity for the blind relative to controls. Source analyses showed comparable solutions in the case of auditory and tactile targets for the blind. These findings support the interpretation of these negativities in terms of a supramodal rather than a modality-specific process, although confirmation with more spatially sensitive methods seems necessary. We additionally examined whether the early blind are less affected by irrelevant tactile or auditory exogenous cues preceding auditory or tactile targets than controls. No differences in alerting and orienting effects of these cues were found between the blind and the controls. Together, our results support the view that major differences between early blind participants and sighted controls on auditory and tactile duration discrimination tasks relate to a late and likely supramodal process that takes place in occipital areas.
Shared Neural Circuits for Mentalizing about the Self and Others
Authors: Lombardo Michael V. , Chakrabarti Bhismadev , Bullmore Edward T. , Wheelwright Sally J. , Sadek Susan A. , Suckling John ,   MRC AIMS Consortium, Baron-Cohen Simon
Published: July 2009

Although many examples exist for shared neural representations of self and other, it is unknown how such shared representations interact with the rest of the brain. Furthermore, do high-level inference-based shared mentalizing representations interact with lower level embodied/simulation-based shared representations? We used functional neuroimaging (fMRI) and a functional connectivity approach to assess these questions during high-level inference-based mentalizing. Shared mentalizing representations in ventromedial prefrontal cortex, posterior cingulate/precuneus, and temporo-parietal junction (TPJ) all exhibited identical functional connectivity patterns during mentalizing of both self and other. Connectivity patterns were distributed across low-level embodied neural systems such as the frontal operculum/ventral premotor cortex, the anterior insula, the primary sensorimotor cortex, and the presupplementary motor area. These results demonstrate that identical neural circuits are implementing processes involved in mentalizing of both self and other and that the nature of such processes may be the integration of low-level embodied processes within higher level inference-based mentalizing.