tbuckley/cabot-search huggingface dataset:
Bevacizumab -- News from the Fast Lane?
Authors: M. Weller, W. K. A. Yung
Journal: Neuro-Oncology (2008)

The introduction of bevacizumab (Avastin), an antibody to the vascular endothelial growth factor (VEGF), into the repertoire of the medical management of malignant gliomas has influenced the area of glioma treatment quite markedly.First, after decades of aiming at stopping tumor growth and being quite satisfied with documenting "stable disease," we are suddenly observing objective response rates at a never-seen frequency exceeding 50%. 1 Admittedly, we have not been convinced by any report that the high response rate translates into a gain in survival.The progression-free survival rate at 6 monthsour current gold standard of assessing novel treatments for recurrent glioblastoma-may be in the range of 40%, but similar figures are also achieved with dose-intense regimens of temozolomide.Second, we may need to reconsider the MacDonald response criteria, which overall have served us well in assessing the efficacy of novel treatments, but which are heavily based on contrast enhancement.Yet in the era of antiangiogenic agents like bevacizumab, which may soon be joined by cilengitide or enzastaurin, altered patterns of recurrence resulting from a change from vessel/ VEGF-dependent growth to vessel/VEGF-independent tumor growth 2 may necessitate the development of new response criteria.Third, and perhaps heralding new patterns of toxicity common to the new class of antiangiogenic agents for glioma treatment, the fear of intratumoral hemorrhages may not have been justified, but craniotomy site dehiscence is increasingly noted as a relevant complication in a minority of glioma patients treated with bevacizumab. 3ourth, the impressive effects of the combination of bevacizumab and irinotecan were unexpected and initially suggested strong synergistic potential for two agents that appeared to have limited activity when administered alone.Yet the results from the first randomized trial of bevacizumab alone versus bevacizumab plus irinotecan presented by Cloughesy and colleagues at the 2008 American Society for Clinical Oncology meeting in Chicago appear to confirm the suspicion that irinotecan is contributing little to the overall effect of this novel regimen.Along these lines, switching patients who progress under bevacizumab and irinotecan to another bevacizumab-containing regimen seems to offer little hope for response. 2Overall survival
Accelerated Restitution of Endothelial Integrity and Endothelium-Dependent Function After phVEGF <sub>165</sub> Gene Transfer
Authors: Takayuki Asahara, Donghui Chen, Yukio Tsurumi, Marianne Kearney, Susan Rossow, Jonathan Passeri, James F. Symes, Jeffrey M. Isner
Journal: Circulation (1996)

Delinquent reendothelialization (rET) has been shown to have a permissive, if not facilitatory, impact on smooth muscle cell proliferation. This inverse relation has been attributed to certain functions of the endothelium, including barrier regulation of permeability, thrombogenicity, and leukocyte adherence, as well as production of growth-inhibitory molecules. Accordingly, the present investigation was designed to test the hypothesis that an endothelial cell (EC) mitogen could serve as the basis for a novel gene therapy strategy designed to facilitate EC regeneration, reduce neointimal thickening, and promote recovery of EC dysfunction after balloon injury.New Zealand White rabbits underwent simultaneous balloon injury and gene transfer of one femoral artery with phVEGF165, encoding the 165-amino acid isoform of vascular endothelial growth factor (VEGF), or pGSVLacZ. In each animal transfected with phVEGF165 or pGSVLacZ, the contralateral femoral artery was also subjected to balloon injury but not to gene transfer. For pGSVLacZ, rET remained incomplete at 4 weeks after transfection; in contrast, phVEGF165 produced prompt rET, which was 95% complete by 1 week. Furthermore, rET in the contralateral, balloon-injured, nontransfected limb of the VEGF group was similarly accelerated. Consequently, intimal thickening was diminished, thrombotic occlusion was less frequent, and recovery of EC-dependent vasomotor reactivity was accelerated in VEGF transfectants compared with control animals. A similar benefit was observed for the contralateral, balloon-injured, nontransfected limb.Catheter-mediated, site-specific arterial gene transfer of phVEGF165 can accelerate rET at local and remote sites, leading to inhibition of neointimal thickening, reduction in thrombogenicity, and restoration of endothelium-dependent vasomotor reactivity. These findings support the notion that gene transfer encoding for an EC-specific mitogen may be useful for preventing the complications, including restenosis, of balloon angioplasty.
Molecular basis for effects of carcinogenic heavy metals on inducible gene expression.
Authors: J W Hamilton, R C Kaltreider, O V Bajenova, M A Ihnat, J McCaffrey, B W Turpie, E E Rowell, J Oh, M J Nemeth, C A Pesce, J P Lariviere
Journal: Environmental Health Perspectives (1998)

Certain forms of the heavy metals arsenic and chromium are considered human carcinogens, although they are believed to act through very different mechanisms. Chromium(VI) is believed to act as a classic and mutagenic agent, and DNA/chromatin appears to be the principal target for its effects. In contrast, arsenic(III) is considered nongenotoxic, but is able to target specific cellular proteins, principally through sulfhydryl interactions. We had previously shown that various genotoxic chemical carcinogens, including chromium (VI), preferentially altered expression of several inducible genes but had little or no effect on constitutive gene expression. We were therefore interested in whether these carcinogenic heavy metals might target specific but distinct sites within cells, leading to alterations in gene expression that might contribute to the carcinogenic process. Arsenic(III) and chromium(VI) each significantly altered both basal and hormone-inducible expression of a model inducible gene, phosphoenolpyruvate carboxykinase (PEPCK), at nonovertly toxic doses in the chick embryo in vivo and rat hepatoma H411E cells in culture. We have recently developed two parallel cell culture approaches for examining the molecular basis for these effects. First, we are examining the effects of heavy metals on expression and activation of specific transcription factors known to be involved in regulation of susceptible inducible genes, and have recently observed significant but different effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. Second, we have developed cell lines with stably integrated PEPCK promoter-luciferase reporter gene constructs to examine effects of heavy metals on promoter function, and have also recently seen profound effects induced by both chromium(VI) and arsenic(III) in this system. These model systems should enable us to be able to identify the critical cis (DNA) and trans (protein) cellular targets of heavy metal exposure leading to alterations in expression of specific susceptible genes. It is anticipated that such information will provide valuable insight into the mechanistic basis for these effects as well as provide sensitive molecular biomarkers for evaluating human exposure.
Tolerance Induction and Autoimmune Encephalomyelitis Amelioration After Administration of Myelin Basic Protein–derived Peptide
Authors: Suzana Marusic, Susumu Tonegawa
Journal: The Journal of Experimental Medicine (1997)

Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is an animal model of paralyzing human disease, multiple sclerosis. EAE is readily induced by immunization with myelin basic protein (MBP) in mice transgenic for an αβ T cell receptor (TCR) that is specific for MBP. Subcutaneous injection of p17 (a peptide consisting of 17 NH2-terminal aminoacids of MBP) in complete Freund's adjuvant (CFA) causes paralysis. Induction of paralysis is inhibited by prior intraperitoneal injection of the same peptide in incomplete Freund's adjuvant (IFA). In addition, ongoing paralysis is ameliorated by subsequent intraperitoneal injection of p17 in IFA. Tolerance induction is equally efficient in Fas-deficient and IL-4–deficient TCR-transgenic mice, suggesting that neither activation-induced cell death nor differentiation into Th2 type cells plays a role in the tolerance induction. Tolerance induction by p17 seems to be based on reduction in the responsiveness of anti-MBP T cells, as documented by lower overall antigen-induced lymphokine production and proliferation, as well as diminished upregulation of early activation marker CD69 by tolerized T cells. We propose that continuous encounters of MBP-specific T cells with p17 play a critical role in the induction and maintenance of tolerance.
Two step mechanisms of tumor selective delivery of N-(2-hydroxypropyl)methacrylamide copolymer conjugated with pirarubicin via an acid-cleavable linkage
Authors: Hideaki Nakamura, Tomas Etrych, Petr Chytil, Manami Ohkubo, Jun Fang, Karel Ulbrich, Hiroshi Maeda
Journal: Journal of Controlled Release (2013)
How to measure renal function in clinical practice: Estimated glomerular filtration rate in general practice
Authors: Jo Richardson
Journal: BMJ (2006)

EDITOR—The introduction of routine reporting of estimated glomerular filtration rate with every serum creatinine requested seems to have led to three outcomes in general practice: worried patients, increased workload, and confused clinicians.1

Although the national service framework for renal services does not say that estimated glomerular filtration rate …
Direct-Reflection Oximetry in Routine Cardiac Catherization
Authors: K. K. BOSSINA, G. A. MOOK, W. G. ZIJLSTRA
Journal: Circulation (1960)

A reflection cuvette oximeter providing instantaneous values has been used in a series of 195 cardiac catheterizations in infants and children. The introduction of this method had considerable influence on the entire catheterization procedure, since the direct availability of fluoroscopic, pressure, and oxygen saturation data allows development of an accurate and complete diagnosis during the catheterization. Six cases, selected because of the important part direct oximetry played in their elucidation, are discussed.
Management of Posterior Reversible Encephalopathy Syndrome Induced by Carfilzomib in a Patient With Multiple Myeloma
Authors: Xuemei Cai, Shamik Bhattacharyya, Anna Plitt, Pooja Raibagkar, Jamie N. LaBuzetta, Stephen M. Schleicher, Nikhil C. Munshi, Joshua P. Klein
Journal: Journal of Clinical Oncology (2014)
Fomites and Herpes Simplex Viruses: A Case for Nonvenereal Transmission?
Authors: John M. Douglas
Journal: JAMA (1983)

Since the earliest reports of genital herpes simplex virus (HSV) infection, questions regarding the frequency of nonvenereal modes of transmission have been raised. In a 1940 report on "Herpes Progenitalis as a Venereal Contagion," Sharlit<sup>1</sup>concluded that "I profoundly trust that none will be so rash as to challenge the claim of celibacy or to impugn the professions of chastity or fidelity on the<i>prima facie</i>evidence of herpes progenitalis." The recognition of HSV-2 as an antigenically distinct strain in the late 1960s, the association between the prevalence of HSV-2 antibody and sexual activity, the high rate of HSV-2 in the partners of patients with genital herpes, and the association between oral-genital contact and the development of genital HSV-1 infection provided conclusive evidence that genital herpes was a sexually transmitted disease.<sup>2-5</sup>In the past several years, stimulated by widespread concern in the sexually active public about the acquisition
Preoperative Cardiac Evaluation and Perioperative Monitoring for Noncardiac Vascular Surgery
Authors: Lee A. Fleisher
Journal: JAMA (1995)

To the Editor.  —The recent article by Dr Mason and colleagues 1 illustrates the advantages of decision analysis in the absence of randomized clinical trials for evaluating the appropriate care of patients with significant coronary artery disease undergoing major vascular surgery. It highlights the multiple confounding factors that would limit the ability to perform such a trial, and it emphasizes the need for large sample size to obtain meaningful data. However, their conclusion that coronary angiography and revascularization are not the optimal strategy except in rare circumstances seems unjustified.  We have recently published a similar decision analysis and concluded that the optimal decision was extremely sensitive to local factors such as morbidity and mortality for both coronary and vascular surgery. 2 The primary difference between our analysis and that of Mason et al is the choice of probability of mortality for the base case. For mortality from abdominal aortic aneurysm
Book: Doctors Afield
Authors: A. Paton
Journal: BMJ (2000)

Eds Mary G McCrea Curnen, Howard Spiro, Deborah St James Yale University Press, £18.50, pp 233 ISBN 0 300 08020 4 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Doctors in Britain are disadvantaged by an education limited to the sciences in order to gain entry to medical school, an obese medical curriculum, and the slavery of house jobs. Thereafter, a busy professional life is dominated by technology and specialisation. There is little time or opportunity to broaden the mind or to talk with patients. It is encouraging, therefore, that the University of Durham has established … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
An 18FDG-PET/CT Finding of a Mediastinal Abscess
Authors: Yvonne Marie Purcell, Chris Hegarty, Osama Sharaf, Aurélie Fabre, Stephen J. Skehan
Journal: Clinical Nuclear Medicine (2013)

A 66-year-old man with left pyriform fossa squamous cell carcinoma (T2N0) was treated with chemoradiation. Nine months later, an emergency tracheostomy was performed for respiratory distress. Contrast-enhanced neck and thorax CT demonstrated a right pyriform mass. FDG-PET/CT showed linear increased uptake extending superiorly from the tracheostomy to the right Eustachian tube and inferiorly to the posterior mediastinum. Postmortem examination confirmed a 7 × 2.2 cm abscess extending from the right parapharyngeal, peritracheal, and prevertebral structures to the mediastinum.
Measuring improvement in dyspnoea: should absolute or relative values be used?
Authors: Miriam J. Johnson, J. Martin Bland, Stephen G. Oxberry, Amy P. Abernethy, David C. Currow
Journal: European Respiratory Journal (2014)

To the Editor: 

The same patient outcome data from clinical trial results, when presented as absolute or relative changes, may appear different in magnitude. Recommendations are to report both absolute and relative, or at least baseline, data from which to calculate absolute values [1, 2]. A systematic review of efficacy trials demonstrated that only relative values were reported in most study abstracts (88%) and the main text (75%) [3].

To inform clinical practice, outcome improvements, whether relative or absolute, must be statistically significant and clinically meaningful. A minimal clinically important difference (MCID) should inform sample size calculations for clinical trials.

Two main methods identify an MCID (distribution and anchor-based methods); ideally used together to interpret one in the context of the other [4]. The distribution method is a statistical calculation based on the baseline variability of the measure in the population studied. This gives an effect size (change after intervention divided by standard deviation of baseline scores), the magnitude of which relates to a small, moderate or large clinical effect [5]. Thus the distribution method can only be used to calculate an absolute MCID as there is no standard deviation of baseline score for a relative measure.

The anchor-based method relates the change in score
Function of HES6 an Inhibitor of HES1, in the Breast Cancer Cell Lines T47D and MCF-7 Is to Up-Regulate E2F-1 and Increased Proliferation.
Authors: A. Strom, J. Hartman, E. Lam, C. Lin, J. Gustafsson, J. Gustafsson
Journal: Cancer Research (2009)

Abstract Hormone resistance remains as a major obstacle in breast cancer treatment. The majority of breast tumors are dependent on estrogens to grow, therefore anti-estrogens such as Tamoxifen is an effective treatment option. We have found that a transcription factor Hes6, earlier described in the nervous tissue, is up-regulated in hormone-independent breast cancer cells compared to normal estrogen sensitive breast cancer cells. By using a lenti-virus system, we have over-expressed Hes6 in T47D cells which are estrogen sensitive. This resulted in increased proliferation. We also found that estrogen treatment of MCF-7 breast cancer cells induced expression of endogenous Hes6 in the G1-phase. We could not find any binding of estrogen receptor α to the HES6 gene but instead found a binding site up-steam of the promoter in the ASCL1 gene. ASCL1 is a known inducer of HES6 and we are showing that ASCL1 is up-regulated by 17β-estradiol in MCF-7 cells. To find the mechanism behind the tumorogenic effects of Hes6, we analysed important factors of the cell-cycle. We found that the G1-phase factor E2F-1 was up-regulated in response to increased Hes6 expression. Since HES6 have been shown to be an inhibitor of HES1, this is in agreement with a previous study where we found that HES1 inhibited proliferation by binding to the promoter of and down-regulating E2F-1 expression. E2F-1 is an important limiting factor in late G1-phase of the cell cycle and can drive cell proliferation.We believe that the HES1-HES6 interplay is important in antiestrogen-resistant breast cancer. Studies are now ongoing to investigate if Hes6 is up-regulated in estrogen-independent human breast cancer samples. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2153.
Treatment of mild gestational diabetes did not prevent neonatal complications but reduced fetal overgrowth
Authors: Denice Feig
Journal: Annals of Internal Medicine (2010)

ACP Journal Club19 January 2010Treatment of mild gestational diabetes did not prevent neonatal complications but reduced fetal overgrowthDenice Feig, MDDenice Feig, MDUniversity of Toronto, Toronto, Ontario, Canada (D.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-2-201001190-02006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLandon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009;361:1339-48. https://pubmed.ncbi.nlm.nih.gov/19797280Clinical Impact RatingsGIM/FP/GP: Endocrinology: Reference1 Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005;352:2477-86. [PMID: 15951574] Google Scholar Author, Article, and Disclosure InformationAuthors: Denice Feig, MDAffiliations: University of Toronto, Toronto, Ontario, Canada (D.F.)This article was published at Annals.org on 5 January 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe use of first and second-generation antipsychotic drugs and the potential to develop gestational diabetes mellitus among perinatal patients with psychosis 19 January 2010Volume 152, Issue 2Page: JC1-6KeywordsBirthGestational diabetesGlucoseHyperinsulinemiaInsulinPreeclampsiaPregnancyRandomized trialsShouldersWeight gain ePublished: 19 January 2010 Issue Published: 19 January 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Correlations Among Autonomic, Sensory, and Motor Neural Function Tests in Untreated Non-insulin-dependent Diabetic Individuals
Authors: Michael A Pfeifer, Clarice R Weinberg, Daniel L Cook, Andrew Reenan, Eugene Halar, Jeffrey B Halter, Edward C LaCava, Daniel Porte
Journal: Diabetes Care (1985)

A well-defined group of untreated non-insulin-dependent (NIDD) subjects were evaluated to determine whether involvement of neural function measurements is generalized and symmetrical and to compare the autonomic, sensory, and motor neural measurements. After age adjustment, the sensory and motor neural function measurements were significantly slower in the diabetic group than in normal subjects (P &amp;lt; 0.01). Similarly, the autonomic nervous system function measurements were also abnormal in the NIDD group (P &amp;lt; 0.01). Further analysis revealed that each of the specific measurements–median motor nerve conduction velocity (NCV, P &amp;lt; 0.005), peroneal motor NCV (P &amp;lt; 0.005), median sensory NCV (P &amp;lt; 0.005), dark-adapted pupil size after muscarinic blockade (P &amp;lt; 0.02), pupillary latency time (P &amp;lt; 0.02), and RR-variation after beta adrenergic blockade (P &amp;lt; 0.001)—was significantly less by analysis of covariance after age adjustment in the NIDD group than in normal subjects. Thus, there was evidence of motor and sensory neural impairment in the upper and lower extremities as well as evidence of impairment of the reflex arcs involving the parasympathetic nerves to the heart and eye and the sympathetic nerves to the iris. Further analysis revealed that right and left NCV were correlated (P &amp;lt; 0.01), as were the median motor and median sensory NCV (P &amp;lt; 0.01), the median motor and peroneal motor NCV (P &amp;lt; 0.001), and the peroneal motor and median sensory NCV (P &amp;lt; 0.001). Thus, there was evidence of symmetrical upper and lower limb, as well as motor and sensory proportional involvement of large nerve fiber NCV in this group of NIDD subjects. Within the autonomic nerve reflex arcs that were tested, the studies showed that there was correlation between measures assessing the reflex arcs involving the parasympathetic nervous system (PNS) to the heart and iris (P &amp;lt; 0.01). However, the measure assessing the sympathetic nervous system (SNS) reflex arc to the iris did not correlate significantly with either of the measures assessing PNS reflexes. Overall, measurements of sensory and motor NCV were correlated with the results of the autonomic nervous system (ANS) tests (P &amp;lt; 0.05). Thus, in a group of untreated NIDD men, age-adjusted measures of SNS, motor (MNS), and ANS function were reduced and there was a correlation between the measures of sensory and motor nerve tests and those of ANS function.