tbuckley/cabot-search huggingface dataset:
Bevacizumab-induced tumor calcifications as a surrogate marker of outcome in patients with glioblastoma
Authors: Oliver Bähr, Elke Hattingen, Johannes Rieger, Joachim P. Steinbach
Journal: Neuro-Oncology (2011)

Therapy-induced calcifications in glioblastoma are rarely recognized. They may represent regressive changes in the tumor tissue, but their occurrence and possible predictive or prognostic value have not been systematically assessed. The observation of hyperintense lesions on precontrast T1-weighted magnetic resonance images (MRIs) in 2 index patients with glioblastoma after therapy with bevacizumab, subsequently identified as calcifications on computed tomographs (CTs), prompted us to prospectively screen for these radiographic changes. Therefore, 36 patients with recurrent glioblastoma prospectively treated with bevacizumab in an observational trial were examined every 8 weeks by MRI and, if clinically necessary, by CT. In 22 patients (61.1%), T1 hyperintense lesions became apparent after bevacizumab treatment. The median time to detection of these lesions was 55 days. In 14 (63.6%) of 22 patients, CTs were available and confirmed the existence of tumor calcifications. No substantial changes in T1 hyperintense lesions or calcifications were recognized on additional MRI or CT scans. Interestingly, the patients with therapy-induced T1 hyperintense lesions had better durations of progression-free survival than patients without these changes (median, 5.8 vs 3.5 months; P< .001), and the duration of overall survival was also superior (median, 9.7 vs 5.0 months; P= .006). There was a striking correlation between the appearance of therapy-induced T1 hyperintense lesions and overall response to bevacizumab. Therefore, this phenomenon is a rather early and time-limited event during the first weeks of treatment and appears to be response related. In summary, T1 hyperintense lesions are common in patients with glioblastoma who have been exposed to bevacizumab, may represent a novel biomarker of response and outcome, and seem to correspond to tumor calcifications.
Gender-Specific Effects of the Catechol- <i>O</i> -Methyltransferase <i>Val</i> <sup>108/158</sup> <i>Met</i> Polymorphism on Cognitive Function in Children
Authors: Jennifer H. Barnett, Jon Heron, Susan M. Ring, Jean Golding, David Goldman, Ke Xu, Peter B. Jones
Journal: American Journal of Psychiatry (2007)

Objective: The study aimed to determine the cognitive effect of the Val 108/158 Met polymorphism in the catechol- O -methyltransferase (COMT) gene in children before and during puberty. This polymorphism affects cognitive function in healthy adults and may contribute to risk for schizophrenia. Method: COMT genotype was determined for 8,707 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), a geographically defined general population cohort of children born between April 1, 1991, and Dec. 31, 1992, in the southwest of England. Fourteen measures of cognitive function—including working memory, verbal and motor inhibition, attentional control, and IQ—were assessed at ages 8 and 10 years. Any pubertal development at age 9 years was reported by parents. Effects of COMT genotype on cognition and interactions with gender and puberty were assessed using general linear models. Results: In boys, genotype significantly affected executive function and explained up to 10 points normal variation in verbal IQ. The effects on IQ were significantly greater in pubertal than in prepubertal boys. In girls, there were no significant effects of genotype on cognition. Conclusions: This common polymorphism may be one of the genes of small effect that contribute to normal variation in IQ. The gender-specific nature of the effect and its possible interaction with puberty may be relevant to both normal cognitive and brain development and to abnormal development in disorders such as schizophrenia.
To PRP or not?
Authors: Lars Engebretsen, Kathrin Steffen
Journal: British Journal of Sports Medicine (2010)

Warm upWas the Super Bowl XLIII really won by platelet-rich plasma (PRP)?In February 2009, Pittsburgh Steelers wide receiver Hines Ward, who suffered a medial knee ligament injury just a week before the big event, caught a pass which helped the Steelers win the Championship.Judging from the press clippings in the USA over the following week, it was PRP, which did it all!The injections jumpstarted the widespread use of PRP we now observe in the USA.Long before this, of course, PRGF (plasma rich in growth factors) had been introduced with much basic and some clinical research for maxillofacial surgery by Dr Eduardo Anitua in Vitoria, Spain. 1 After fi rst having published impressive results from his own research fi eld, his group followed up with the fi rst studies in sports medicine as well. 2 In 2007, Peter A M Everts from Eindhoven in The Netherlands defended his impressive thesis on 'Autologous platelet-leucocyte enriched gel.Basics and effi cacy,' 3 where he used the system to support soft tissue and bone healing.We urge users of PRP to read the original works by Anitua and Everts fi lled with historic and recent science on PRP.
Barrett's oesophagus: epidemiology, cancer risk and implications for management
Authors: Pieter Jan F de Jonge, Mark van Blankenstein, William M Grady, Ernst J Kuipers
Journal: Gut (2013)

Although endoscopic surveillance of patients with Barrett9s oesophagus has been widely implemented, its effectiveness is debateable. The recently reported low annual oesophageal adenocarcinoma risk in population studies, the failure to identify most Barrett9s patients at risk of disease progression, the poor adherence to surveillance and biopsy protocols, and the significant risk of misclassification of dysplasia all tend to undermine the effectiveness of current management, in particular, endoscopic surveillance programmes, to prevent or improve the outcomes of patients with oesophageal adenocarcinoma. The ongoing increase in incidence of Barrett9s oesophagus and consequent growth of the surveillance population, together with the associated discomfort and costs of endoscopic surveillance, demand improved techniques for accurately determining individual risk of oesophageal adenocarcinoma. More accurate techniques are needed to run efficient surveillance programmes in the coming decades. In this review, we will discuss the current knowledge on the epidemiology of Barrett9s oesophagus, and the challenging epidemiological dilemmas that need to be addressed when assessing the current screening and surveillance strategies.
Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
Authors: Efthimia Karantzali, Herbert Schulz, Oliver Hummel, Norbert Hubner, AK Hatzopoulos, Androniki Kretsovali
Journal: Genome biology (2008)

Abstract Background Epigenetic mechanisms regulate gene expression patterns affecting cell function and differentiation. In this report, we examine the role of histone acetylation in gene expression regulation in mouse embryonic stem cells employing transcriptomic and epigenetic analysis. Results Embryonic stem cells treated with the histone deacetylase inhibitor Trichostatin A (TSA), undergo morphological and gene expression changes indicative of differentiation. Gene profiling utilizing Affymetrix microarrays revealed the suppression of important pluripotency factors, including Nanog, a master regulator of stem cell identity, and the activation of differentiation-related genes. Transcriptional and epigenetic changes induced after 6-12 hours of TSA treatment mimic those that appear during embryoid body differentiation. We show here that the early steps of stem cell differentiation are marked by the enhancement of bulk activatory histone modifications. At the individual gene level, we found that transcriptional reprogramming triggered by histone deacetylase inhibition correlates with rapid changes in activating K4 trimethylation and repressive K27 trimethylation of histone H3. The establishment of H3K27 trimethylation is required for stable gene suppression whereas in its absence, genes can be reactivated upon TSA removal. Conclusion Our data suggest that inhibition of histone deacetylases accelerates the early events of differentiation by regulating the expression of pluripotency- and differentiation-associated genes in an opposite manner. This analysis provides information about genes that are important for embryonic stem cell function and the epigenetic mechanisms that regulate their expression.
The Small Congenital Nevocytic Nevus and Malignant Melanoma
Authors: M. Barry Kirschenbaum
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Malignant melanoma has been reported to occur in the large "bathing trunk nevus" in up to 20% of patients. The small congenital nevus has been looked on for years as a benign lesion that could be ignored. During recent years a great deal of discussion has occurred at local and national meetings concerning the transformation of small nevocytic nevi, which were present at birth, into melanomas. There is to date little evidence that this does, indeed, occur, except for occasional case histories. To gain some insight into this problem, I would appreciate reading case histories where the change from small congenital nevus to malignant melanoma has been noted. I would appreciate knowing age of onset, size, location, outcome, and race of the patient.
Psychometric issues associated with computerised neuropsychological assessment of concussed athletes
Authors: A Collie, P Maruff, M McStephen, D G Darby
Journal: British Journal of Sports Medicine (2003)

Psychometric issues associated with computerised neuropsychological assessment in sports concussion are put forward. Issues critical to ensuring test reliability and sensitivity are discussed, with particular reference to how inappropriate test design can affect clinical decision making.
Atorvastatin and Celecoxib Inhibit Prostate PC-3 Tumors in Immunodeficient Mice
Authors: Xi Zheng, Xiao-Xing Cui, Gina E. Avila, Mou-Tuan Huang, Yue Liu, Jagruti Patel, Ah Ng Tony Kong, Raphael Paulino, Weichung Joe Shih, Yong Lin, Arnold B. Rabson, Bandaru S. Reddy, Allan H. Conney
Journal: Clinical Cancer Research (2007)

To investigate the effects and mechanisms of atorvastatin and celecoxib administered individually or in combination on human prostate cancer PC-3 cells cultured in vitro or grown as xenograft tumors in immunodeficient mice.Human prostate cancer PC-3 cells in culture were treated with atorvastatin and celecoxib alone or in combination. Severe combined immunodeficient (SCID) mice were injected s.c. with PC-3 cells. The mice received daily i.p injections starting 2 days before tumor cell inoculation and continuing during the course of treatment with atorvastatin (10 microg/g body weight/d), celecoxib (10 microg/g/d), a combination of atorvastatin (10 microg/g/d) and celecoxib (10 microg/g/d), or a combination of atorvastatin (5 microg/g/d) and celecoxib (5 microg/g/d).Atorvastatin in combination with celecoxib had stronger effects on growth inhibition and apoptosis of PC-3 cells than either agent used individually. Atorvastatin and celecoxib in combination also had a stronger inhibitory effect on activation of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 in PC-3 cells than either agent alone. Treatment of SCID mice with combinations of atorvastatin and celecoxib more effectively inhibited the formation and growth of PC-3 tumors in the mice than either agent administered alone.A combination of atorvastatin and celecoxib had a more potent inhibitory effect on the growth of PC-3 cells cultured in vitro or grown in SCID mice than either agent alone. A combination of atorvastatin and celecoxib may be an effective strategy for the prevention of prostate cancer.
Can traffic-related air pollution cause asthma?
Authors: J. R Balmes
Journal: Thorax (2009)

Traffic-generated pollution contains particles and gases (eg, oxides of nitrogen) that are known to have health effects.1 Concentrations of pollutants emitted by motor vehicles are highest within 150 m of roadways and remain raised up to 300 m from roadways, but fall off markedly beyond that range.2 3 Exposure to the mixture of traffic-generated pollutants may be more relevant to human health than exposure to any single ambient air pollutant, making epidemiological investigations of traffic effects a key component of research into the public health impact of air pollution. However, assessment of exposure to traffic-related air pollution can be problematic. Exposure to traffic can be estimated with complex dispersion models of pollutants from local freeway and non-freeway sources, but the data inputs required for such modelling are not always available. A frequently used simpler approach has been to estimate residential distance to roadways.

A number …
Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia
Authors: Renée Beekman, Marijke G. Valkhof, Mathijs A. Sanders, Paulette M. H. van Strien, Jurgen R. Haanstra, Lianne Broeders, Wendy M. Geertsma-Kleinekoort, Anjo J. P. Veerman, Peter J. M. Valk, Roel G. Verhaak, Bob Löwenberg, Ivo P. Touw
Journal: Blood (2012)
Physical Training Increases eNOS Vascular Expression and Activity and Reduces Restenosis After Balloon Angioplasty or Arterial Stenting in Rats
Authors: Ciro Indolfi, Daniele Torella, Carmela Coppola, Antonio Curcio, Francisca Rodriguez, Antonio Bilancio, Antonio Leccia, Oreste Arcucci, Mariacristina Falco, Dario Leosco, Massimo Chiariello
Journal: Circulation Research (2002)

The effects of dynamic exercise on restenosis after vascular injury are still unknown. The consequences of balloon dilation–induced injury on neointimal hyperplasia, vascular negative remodeling, and reendothelialization were assessed in sedentary and trained rats. Ex vivo eNOS vascular expression and activity were investigated in carotid arteries isolated from sedentary and exercised rats. The in vivo effects of eNOS inhibition by L-NMMA on vessel wall after balloon dilation were evaluated in sedentary and exercised rats. We also investigated the effects of exercise on neointimal formation in a rat stent model of vascular injury. Compared with sedentary group, the arteries isolated from trained rats showed higher levels of eNOS protein expression and activity 7 days after balloon dilation. A significant reduction of both neointimal hyperplasia and negative remodeling was observed 14 days after balloon injury in trained compared with sedentary rats. Moreover, we demonstrated that exercise training produced accelerated reendothelialization of the balloon injured arterial segments compared with sedentary. L-NMMA administration eliminated the benefits of physical training on vessel wall after balloon dilation. Finally, a decrease of neointimal hyperplasia as well as of platelet aggregation was observed after stent deployment in trained rats compared with sedentary. In conclusion, physical exercise could favorably affect restenosis after balloon angioplasty and stenting. Increase in eNOS expression and activity might contribute to the potential beneficial effects of exercise on the vessel wall after vascular injury.
Effect of alteration of left ventricular activation sequence on the left ventricular end-systolic pressure-volume relation in closed-chest dogs.
Authors: R C Park, W C Little, R A O'Rourke
Journal: Circulation Research (1985)

We investigated the effect of pacing from the atrium and various ventricular sites on the left ventricular end-systolic pressure-volume relation following autonomic blockade in a total of 10 dogs chronically instrumented to measure left ventricular pressure and determine left ventricular volume from three ultrasonic endocardial dimensions. During ventricular pacing, left ventricular end-diastolic volume, stroke volume, and end-systolic pressure were decreased, while the end-systolic volume was relatively unchanged. Left ventricular end-systolic pressure-volume relations were generated by vena caval occlusions during pacing at a constant rate from the left atria, and the epicardium of the right ventricular free wall, right ventricular apex, and left ventricular free wall. The left ventricular end-systolic pressure-volume relations were described by straight lines for each site (r greater than 0.96 and SEE less than 2.9 mm Hg in all but one instance). Compared to atrial pacing, the left ventricular end-systolic pressure-volume relations were shifted (P less than 0.001) to the right during pacing from ventricular sites. During atrial pacing, the volume intercept of the left ventricular end-systolic pressure-volume relation was 16.0 +/- 7.2 ml (mean +/- SD), and increased to 18.7 +/- 7.8 ml (P less than 0.05) during pacing from the right ventricular free wall, to 19.6 +/- 7.7 ml (P less than 0.05) during pacing from the right ventricular apex, and to 20.0 +/- 7.5 ml (P less than 0.05) during pacing from the left ventricular free wall. These volume intercepts correlated roughly with the extent of dyssynchronous activation as estimated by the QRS duration (r = 0.59 to 0.93) and the time for left ventricular endocardial activation (r = 0.92 and 0.95). During ventricular pacing, the slope of the left ventricular end-systolic pressure-volume relation changed only slightly. Similar results were obtained during pacing from right ventricular endocardial sites. We conclude that alterations of the normal activation sequence produced by ventricular pacing depress left ventricular pumping function independent of loading conditions, as indicated by a rightward shift of the left ventricular end-systolic pressure-volume relation. The extent of this shift appears to be in proportion to the degree of dyssynchronous activation. The decreased stroke volume during ventricular pacing is due both to a decreased end-diastolic volume (decreased preload) and the rightward shift of the end-systolic pressure-volume relation (decreased pump function).
Systemic and local factors are involved in the evolution of erosions in hand osteoarthritis
Authors: J. Bijsterbosch, J. M. van Bemmel, I. Watt, I. Meulenbelt, F. R. Rosendaal, T. W. J. Huizinga, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated. <h3>Methods</h3> The 6-year evolution in radiographic Verbruggen–Veys anatomical phase was assessed in interphalangeal joints of 236 patients with hand OA (mean age 59 years, 83% women) from the GARP (for 'Genetics ARthrosis and Progression') sibling pair study. Erosive evolution comprised phase transitions from non-erosive to erosive phases and from active erosions to remodelling. Clustering of erosive evolution within patients was assessed using the χ<sup>2</sup> test. Familial aggregation was evaluated in sibling pairs by estimating ORs for siblings and probands sharing erosive evolution. Local baseline determinants and the effect of high sensitivity C reactive protein were assessed using generalised estimating equations. <h3>Results</h3> Erosive evolution took place in 181 of 4120 interphalangeal joints at risk (4.4%), corresponding to 60 patients (25.4% of study sample). Erosive evolution was found more often in multiple interphalangeal joints in one patient than would be expected by chance (χ<sup>2</sup> 373.0, p&lt;0.001). The adjusted OR (95% CI) for a sibling having erosive evolution if the proband had erosive evolution was 4.7 (1.4 to 15.8). Systemic inflammation was not associated with erosive activity. Independent local determinants were joint space narrowing (OR (95% CI) 8.9 (4.8 to 16.4)) and self-reported pain (OR (95%CI) 2.3 (1.1 to 4.7)). <h3>Conclusions</h3> Erosive evolution was clustered within patients and families. Local factors were also involved in the evolution. This increase in insight in the pathogenesis of erosive hand OA will contribute to the development of new treatments.
Review and Critique of the New DSM-IV Diagnosis of Acute Stress Disorder
Authors: Randall D. Marshall, Robert Spitzer, Michael R. Liebowitz
Journal: American Journal of Psychiatry (1999)

A new diagnosis can greatly influence scientific research, access to resources, and treatment selection in clinical practice. The authors review the historical evolution, rationale, empirical foundation, and clinical utility to date of the recently introduced diagnosis of acute stress disorder.The conceptual basis and relevant methods for identifying a psychiatric syndrome are reviewed with respect to acute stress disorder, including selection of criteria for core symptoms; considerations of sensitivity and specificity of a syndrome definition; longitudinal course; and distinctions between normative and pathological phenomena. Particular attention is devoted to two major issues: the implications of the core feature requirement of three of five dissociative symptoms, and the question of whether there should be two separate diagnoses (acute stress disorder and post-traumatic stress disorder [PTSD]) describing posttraumatic syndromes. The widely divergent approaches in DSM-IV and ICD-10 are also reviewed.The diagnosis of acute stress disorder does not appear to achieve the important objective of providing adequate clinical coverage for individuals with acute posttraumatic symptoms. The validity and utility of requiring peritraumatic dissociative symptoms as a core feature are questionable, as is the separation of essentially continuous clinical phenomena into two disorders with different criteria sets (acute stress disorder and PTSD) based on persistence of symptoms for 30 or more days.Longitudinal studies using acute stress disorder criteria, as well as broader considerations of the clinical and scientific functions that posttraumatic diagnoses should serve, suggest a need to reevaluate the current DSM-IV approach to posttraumatic syndromes.