tbuckley/cabot-search huggingface dataset:
Abstract 2528: Vardenafil is superior to idarubicin in treatment of glioma
Authors: Abdelkader E. Ashour, Abdulrahman Z. Alzahrani, Hala E. Abdel-Hamied, Khairy M. Zoheir, Sheikh F. Ahmed, Salem S. Al-Rejaie, Adel R. Abd-Allah
Journal: Cancer Research (2015)

Abstract Idarubicin (IDA) is a very potent second generation anthracycline that has shown high efficacy against glioma in vitro. However, this agent has failed to exert satisfactory therapeutic response in patients with brain tumors. Phosphodiesterase (PDE-5), an enzyme which hydrolyzes intracellular cyclic guanosine monophosphate (cGMP), is highly expressed in many brain tumor cell lines. We proposed that increasing cGMP in the brain by the potent PDE-5 inhibitor vardenafil (VAR) will augment the antitumor efficacy of IDA against glioma. We also proposed that VAR will induce apoptosis of glioma cells. Here we show for the first time that VAR (10 mg/kg) enhanced the antitumor activity of IDA (0.1mg/kg). VAR alone inhibited tumor growth and prolonged survival of glioma bearing rats. Histopathological examination revealed that tumors from glioma bearing rats treated with VAR alone or VAR+ IDA presented a significant reduction in mitotic index, indicating less proliferative tumors, as compared to those which received PBS (control) or IDA. Real time PCR results demonstrated that VAR inhibited mRNA expression of PDE-5 in the brains of animals treated with VAR, compared to control-treated group, implicating an important role for the inhibition of PDE-5 in the antitumor activity of VAR. Interestingly, the antitumor activity of VAR was similar to that of IDA. Moreover, animals receiving either VAR alone or VAR+IDA demonstrated statistically significant improvement in overall survival when compared with control (PBS) or IDA groups. In order to explain such an unexpected finding, we examined the antiproliferative, pro-apoptotic and anti-invasive activities VAR in vitro. MTT assay results showed that VAR significantly inhibited the growth of rat C6 glioma cells. Annexin V propidium iodide assay results revealed that the inhibition of C6 cell growth is mediated at least in part by inducing C6 apoptosis. Wound healing and soft agar colony formation assays showed that VAR inhibited the migration and anchorage-independent growth of C6 cells, respectively. This suggests that the enhanced antitumor effect of VAR could be due to a combined antiproliferative, pro-apoptotic and anti-invasive activities. Together, our data support anti-glioma properties of VAR, and provide a proof-of-concept basis for further development of VAR as potential adjuvant for treatment of brain tumors. Citation Format: Abdelkader E. Ashour, Abdulrahman Z. Alzahrani, Hala E. Abdel-Hamied, Khairy M. Zoheir, Sheikh F. Ahmed, Salem S. Al-Rejaie, Adel R. Abd-Allah. Vardenafil is superior to idarubicin in treatment of glioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2528. doi:10.1158/1538-7445.AM2015-2528
Bronchial Artery Angiogenesis Drives Lung Tumor Growth
Authors: Lindsey Eldridge, Aigul Moldobaeva, Qiong Zhong, John Jenkins, Michael Snyder, Robert H. Brown, Wayne Mitzner, Elizabeth M. Wagner
Journal: Cancer Research (2016)

Angiogenesis is vital for tumor growth but in well-vascularized organs such as the lung its importance is unclear. This situation is complicated by the fact that the lung has two separate circulations, the pulmonary and the systemic bronchial circulation. There are few relevant animal models of non-small cell lung cancer, which can be used to study the lung's complex circulations, and mice, lacking a systemic bronchial circulation cannot be used. We report here a novel orthotopic model of non-small cell lung cancer in rats, where we have studied the separate contributions of each of the two circulations for lung tumor growth. Results show that bronchial artery perfusion, quantified by fluorescent microspheres (206% increase in large tumors) or high-resolution computed tomography scans (276% increase in large tumors), parallels the growth in tumor volume, whereas pulmonary artery perfusion remained unchanged. Ablation of the bronchial artery after the initiation of tumor growth resulted in a decrease in tumor volume over a subsequent course of 4 weeks. These results demonstrate that although the existing pulmonary circulation can supply the metabolic needs for tumor initiation, further growth of the tumor requires angiogenesis from the highly proliferative bronchial circulation. This model may be useful to investigate new therapeutic approaches that target specifically the bronchial circulation. Cancer Res; 76(20); 5962-9. ©2016 AACR.
LAW AND MEDICINE
Authors: Angela Roddey Holder
Journal: JAMA (1971)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Use of Stem Cells for Ischemic Cardiomyopathy—Reply
Authors: Joshua M. Hare, Darcy Difede, Alan W. Heldman
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Changing Incidence of Thyroid Cancer
Authors: H. Gilbert Welch, Louise Davies
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Availability and Use of HIV Monitoring and Early Infant Diagnosis Technologies in WHO Member States in 2011–2013: Analysis of Annual Surveys at the Facility Level
Authors: Vincent Habiyambere, Nathan Ford, Daniel Low-Beer, John Nkengasong, Anita Sands, Mercedes Pérez González, Paula Fernandes, Ekaterina Milgotina
Journal: PLoS Medicine (2016)

Background The Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets have reinforced the importance of functioning laboratory services to ensure prompt diagnosis and to assess treatment efficacy. We surveyed the availability and utilization of technologies for HIV treatment monitoring and early infant diagnosis (EID) in World Health Organization (WHO) Member States. Methods and Findings The survey questionnaire included 14 structured questions focusing on HIV testing, cluster of differentiation 4 (CD4) testing, HIV viral load (VL) testing, and EID and was administered annually from 2012 to 2014 through WHO country offices, with each survey covering the previous 12-mo period. Across 127 targeted countries, survey response rates were 60% in 2012, 67% in 2013, and 78% in 2014. There were encouraging trends towards increased procurement of CD4 and VL/EID instruments in reporting countries. Globally, the capacity of available CD4 instruments was sufficient to meet the demand of all people living with HIV/AIDS (PLWHA), irrespective of treatment status (4.62 theoretical tests per PLWHA in 2013 [median 7.33; interquartile range (IQR) 3.44–17.75; median absolute deviation (MAD) 4.35]). The capacity of VL instruments was inadequate to cover all PLWHA in many reporting countries (0.44 tests per PLWHA in 2013 [median 0.90; IQR 0.30–2.40; MAD 0.74]). Of concern, only 13.7% of existing CD4 capacity (median 4.3%; IQR 1.1%–12.1%; MAD 3.8%) and only 36.5% of existing VL capacity (median 9.4%; IQR 2.3%–28.9%; MAD 8.2%) was being utilized across reporting countries in 2013. By the end of 2013, 7.4% of all CD4 instruments (5.8% CD4 conventional instruments and 11.0% of CD4 point of care [POC]) and 10% of VL/EID instruments were reportedly not in use because of lack of reagents, the equipment not being installed or deployed, maintenance, and staff training requirements. Major limitations of this survey included under-reporting and/or incomplete reporting in some national programmes and noncoverage of the private sector. Conclusion This is the first attempt to comprehensively gather information on HIV testing technology coverage in WHO Member States. The survey results suggest that major operational changes will need to be implemented, particularly in low- and middle-income countries, if the 90-90-90 targets are to be met.
Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates
Authors: Chelsie K Sievers, Luli S Zou, Perry J Pickhardt, Kristina A Matkowskyj, Dawn M Albrecht, Linda Clipson, Jeffery W Bacher, B Dustin Pooler, Fouad J Moawad, Brooks D Cash, Mark Reichelderfer, Tien N Vo, Michael A Newton, Bret R Larget, Richard B Halberg
Journal: Gut (2016)

Objective and design The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6–9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modelling and statistical inference considering several parameters including allele frequency and fitness. Results The mutational landscape of small polyps is varied both within individual polyps and among the group as a whole but no single alteration was correlated with growth behaviour. Polyps carried 0–3 pathogenic mutations with the most frequent being in APC , KRAS/NRAS , BRAF , FBXW7 and TP53 . In polyps with two or more pathogenic mutations, allele frequencies were often variable, indicating the presence of multiple populations within a single tumour. Based on computer modelling, detectable mutations occurred at a mean polyp size of 30±35 crypts, well before the tumour is of a clinically detectable size. Conclusions These data indicate that small colon polyps can have multiple pathogenic mutations in crucial driver genes that arise early in the existence of a tumour. Understanding the molecular pathway of tumourigenesis and clonal evolution in polyps that are at risk for progressing to invasive cancers will allow us to begin to better predict which polyps are more likely to progress into adenocarcinomas and which patients are at greater risk of developing advanced disease.
Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis
Authors: Johan W Verjans, Eric A Osborn, Giovanni J Ughi, Marcella A Calfon Press, Ehsan Hamidi, Antonios P Antoniadis, Michail I Papafaklis, Mark F Conrad, Peter Libby, Peter H Stone, Richard P Cambria, Guillermo J Tearney, Farouc A Jaffer
Journal: JACC. Cardiovascular imaging (2016)
Comparative analysis of the representative value of somatic mutation profiles derived from ctDNA and other updated lung tumor biopsy alternative in non-resectable non-small cell lung cancer patients.
Authors: Xiaozheng Kang, Ting Xu, Ting Zhou, De-Qun Tian, Grace Q. Zhao, Shengrong Lin, Kang Ying, Guo-Bing Xu, Ke-Neng Chen
Journal: Journal of Clinical Oncology (2016)

e23034 Background: Genomic profiling is critical for optimal treatment selection in non-small cell lung cancer (NSCLC) patients. Unfortunately, a number of these patients are ill-suited for tissue biopsy. While tumors under formalin fixation and paraffin embedding (FFPE) from prior sampling or lymph node biopsy may provide alternatives to update lung tumor biopsy, genomic profiles generated from these sources may not best represent a patient’s current condition. Here, we compare circulating tumor DNA (ctDNA) to DNA acquired from either tumor biopsy or a biopsy alternative to assess their comparative representative value. Methods: Plasma samples were collected from 20 non-resectable NSCLC patients and subject to NGS ctDNA analysis using Accu-Act, a panel of 61 genes with implications in cancer treatment. Parallel sequencing was performed on tumor tissue derived from update lung tumor biopsy or alternatives. Of the 20 tumor tissue samples, 7 came from old FFPE samples, 4 from recent lymph node biopsy, 8 from recent tumor biopsy, and 1 from recent needle biopsy. Concordance of ctDNA and tumor/lymph node gDNA was determined and mutation profiles were correlated with the patient’s treatment progression. Results: Of the 7 FFPE samples, 3 showed good concordance (90%) with cfDNA mutation profiles. No concordance was found for gDNA derived from recent lymph node biopsy. Among the 14 patients undergoing EGFR-TKI treatment, their respective ctDNA mutation profiles correlated with their current status including 2 patients determined as partial response had clearly suppressed EGFR mutations; 2 out of 6 patients determined as progressive disease, had known EGFR drug-resistant mutations. Conclusions: From this small comparative analysis, we demonstrate the superiority of cfDNA profiling in providing a more accurate representation of a patient’s cancer progression relative to genomic profiling performed on alternative genomic sources in patients with non-resectable NSCLC. In addition, our finding suggests treatment prediction using ctDNA profiling is superior to profiling performed on gDNA from alternatives to biopsy.
Use of ibuprofen in paediatric populations.
Authors: van den Anker Jn
Journal: Journal of the Royal Society of Medicine (2007)

In the paediatric population, ibuprofen and paracetamol are both commonly used over-the-counter (OTC) drugs for the management of fever or mild-to-moderate pain associated with sore throat, toothache, earache and headache. Paediatric formulations of ibuprofen and paracetamol are included in the World Health Organization (WHO) Essential Drug List, where they are indicated for both analgesic and antipyretic use. Ibuprofen, originally licensed as a prescription drug for children in 1989, was approved for OTC use in the USA in 1995. The WHO-recommended dose of ibuprofen is 5–10 mg/kg orally every 6–8 hours, to a maximum of 500 mg/day.1 For paracetamol, the WHO recommended dose is 10–15 mg/kg every 4 hours.1 The standard recommended doses for both drugs in the UK are presented in Table 1. Aspirin is not recommended in children 416 years of age owing to its implication in the development of Reye’s syndrome.2
Arboviral and other illnesses in travellers returning from Brazil, June 2013 to May 2016: implications for the 2016 Olympic and Paralympic Games
Authors: Philippe Gautret, Frank Mockenhaupt, Martin P Grobusch, Camilla Rothe, Frank von Sonnenburg, Perry J van Genderen, Francois Chappuis, Hilmir Asgeirsson, Eric Caumes, Emmanuel Bottieau, Denis Malvy, Rogelio Lopez-Vélez, Mogens Jensenius, Carsten Schade Larsen, Francesco Castelli, Christophe Rapp, Vanessa Field, Israel Molina, Effrossyni Gkrania-Klotsas, Simin Florescu, David Lalloo, Patricia Schlagenhauf
Journal: Eurosurveillance (2016)

We evaluated EuroTravNet (a GeoSentinel subnetwork) data from June 2013 to May 2016 on 508 ill travellers returning from Brazil, to inform a risk analysis for Europeans visiting the 2016 Olympic and Paralympic Games in Brazil. Few dengue fever cases (n = 3) and no cases of chikungunya were documented during the 2013–15 Brazilian winter months, August and September, the period when the Games will be held. The main diagnoses were dermatological (37%), gastrointestinal (30%), febrile systemic illness (29%) and respiratory (11%).
THE PROBLEM OF THE NEUROTIC PATIENT
Authors: W C MENNINGER
Journal: Annals of Internal Medicine (1947)

Article1 October 1947THE PROBLEM OF THE NEUROTIC PATIENTWILLIAM C. MENNINGER, M.D., F.A.C.P.WILLIAM C. MENNINGER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-27-4-487 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe title of my paper, "The Problem of the Neurotic Patient," does not make clear whether the patient or the doctor has a problem. Actually they both have: to the patient his neurotic illness is a problem, to the doctor the diagnosis and treatment of that illness are often a problem.As a psychiatrist, I represent a minority of the medical practitioners. However, the subject of my discussion, "the neurotic patient," represents a majority of all of the patients who seek help from physicians. This fact is not new but military experience gave dramatic evidence to support it. The discharges... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Topeka, Kansas*Presented at the Twenty-Eighth Annual Session, American College of Physicians, Chicago, April 28, 1947. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1947Volume 27, Issue 4Page: 487-493KeywordsArmed forces Issue Published: 1 October 1947 Copyright & PermissionsCopyright, 1947, by The American College of PhysiciansPDF downloadLoading ...
Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost Trial
Authors: Conny Vrieling, Erik van Werkhoven, Philippe Maingon, Philip Poortmans, Caroline Weltens, Alain Fourquet, Dominic Schinagl, Bing Oei, Carla C. Rodenhuis, Jean-Claude Horiot, Henk Struikmans, Erik Van Limbergen, Youlia Kirova, Paula Elkhuizen, Rudolf Bongartz, Raymond Miralbell, David A. L. Morgan, Jean-Bernard Dubois, Vincent Remouchamps, René-Olivier Mirimanoff, Guus Hart, Sandra Collette, Laurence Collette, Harry Bartelink
Journal: JAMA Oncology (2016)

Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy.The EORTC "boost no boost" trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up.Participants included 5569 early-stage breast cancer patients, treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI), who were randomized between no boost and a 16-Gy boost in the EORTC phase III "boost no boost" trial (1989-1996). A total of 1616 patients with a microscopically complete resection (according to local pathologists), included in the central pathology review, have been analyzed in this study. Median follow-up was 18.2 years.No further treatment or 16-Gy boost, after BCS and 50-Gy WBI.Time to ipsilateral breast tumor recurrence (IBTR) as first event.The 20-year cumulative incidence of IBTR in 1616 patients (160 events observed) was 15% (95% CI, 12%-17%). Young age (P < .001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI, 1.36-3.38; P = .001) were associated with an increased risk of IBTR in multivariable analysis. The cumulative incidence of IBTR at 20 years was 34% (95% CI, 25%-41%), 14% (95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40 years or younger, 41 to 50 years and 50 years or older, respectively (P < .001). This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with and without DCIS (P < .001). High-grade tumors relapsed more frequently early during follow-up but the relative effect of age and presence of DCIS seemed stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI, 22%-39%) to 15% (95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P < .001) in high-risk patients (≤50 years with DCIS present).The association of high-grade invasive tumor with IBTR diminished during follow-up, while the effect of DCIS adjacent to invasive tumor seemed to remain stable. Therefore, patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years, while additional DCIS is an indication for longer follow-up, emphasizing the importance of long-term trial follow-up to estimate absolute effects accurately.clinicaltrials.gov Identifier: NCT02295033.