tbuckley/cabot-search huggingface dataset:
Abstract 1756: Novel irreversible EGFR tyrosine kinase inhibitor, DBPR112, as a therapeutic candidate for lung adenocarcinoma
Authors: Hui-Yi Shiao, Tsu-An Hsu, Wen-Hsing Lin, Tsong-Toh Yang, Hui-Fang Hsieh, Chiung-Tong Chen, Teng-Kuang Yeh, Hsing-Pang Hsieh
Journal: Cancer Research (2014)

Abstract Lung cancer is the leading cause of cancer death in the world and non-small cell lung cancer (NSCLC) accounts for 85% of the lung cancer deaths. In recent years, EGFR tyrosine kinase inhibitors (TKIs) have showed remarkable effects in patients with certain genetic alternations in the EGFR proteins. However, the clinical benefits of two first-generation EGFR TKIs (gefitinib and erlotinib) have been limited due to the acquired resistance from patients within 9-12 months after treatment, therefore, the discovery of next-generation EGFR-TKIs poses an utmost priority. Our team at IBPR has identified DBPR112 as a potent EGFR-TKI, showing IC50 of 2 nM in HCC827 cells, EGFRWild-Type (IC50: 10 nM) and EGFRL858R/T790M (IC50: 70 nM), which are comparatively better than gefitinib and similar to that of BIBW2992 (afatinib, developed by Boehringer Ingelheim, and approved by FDA in 2013). DBPR112 (10, 50 and 100 mg/kg/day, 5 days/wk for 2 weeks) was orally effective against the growth of human lung HCC827 tumors subcutaneously xenografted in nude mice. A dramatic reduction in tumor size was noted with DBPR112 treatment at 50 and 100 mg/kg/day, while displaying negligible body weight loss in all dosing groups. In addition, the pharmacokinetics properties of DBPR112 are superior to those of BIBW2992; demonstrating the potential of DBPR112 as a therapeutic candidate for the treatment of lung adenocarcinoma with EGFR mutations. This NRPB-granted 4-year top-down project was commenced in Dec. 2012 and aimed at accomplishing a comprehensive program of pre-clinical development and phase I study. To date, several pre-clinical studies and progress were steadily accomplished, including non-GMP production of 5 kg DBPR112 (tox-lot), preliminary analysis methods development, pre-formulation study, pharmacokinetics/metabolism studies and preliminary toxicology evaluation. GLP-toxicity studies, GMP-production of DBPR112 (clinical-lot) and formulation for clinical use will be scheduled in 2014 (2nd year of this top-down project), and we look forward to filing an IND application in early 2015. Citation Format: Hui-Yi Shiao, Tsu-An Hsu, Wen-Hsing Lin, Tsong-Toh Yang, Hui-Fang Hsieh, Chiung-Tong Chen, Teng-Kuang Yeh, Hsing-Pang Hsieh. Novel irreversible EGFR tyrosine kinase inhibitor, DBPR112, as a therapeutic candidate for lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1756. doi:10.1158/1538-7445.AM2014-1756
Abstract 753: Assessment of Atrial Septal Defect Anatomy by Real-Time Three-dimensional Transesophageal Echocardiography and Residual Shunting After Transcatheter Atrial Septal Defect Closure
Authors: Amer M Johri, Igor F Palacios, Roberto J Cubeddu, Ignacio Inglessis, Jonathan Passeri
Journal: Circulation (2009)
Trazodone in the treatment of panic disorder and agoraphobia with panic attacks
Authors: M Mavissakalian, J Perel, K Bowler, R Dealy
Journal: American Journal of Psychiatry (1987)

Eleven patients with panic disorder or agoraphobia with panic attacks completed an 8-week single-blind trial of trazodone (300 mg/day) without concurrent behavioral instructions. The measures of change included ratings of generalized and panic anxiety, phobias, and depression and a behavioral avoidance test, which were administered during a baseline period of placebo administration and at 4 and 8 weeks of the trial. There was significant improvement on all symptom dimensions, which suggests that trazodone may have specific antipanic and antiphobic actions and underscores the importance of serotonergic mechanisms in these anxiety disorders.
Toys and games: poorly recognised hearing hazards?
Authors: L. M Luxon
Journal: BMJ (1998)

In 1995 the World Health Organisation estimated that 120 million people worldwide had a disabling hearing impairment.1 Many causes of hearing impairment are recognised, but noise exposure in childhood has been largely ignored.

There is evidence to suggest that children's hearing is particularly vulnerable to noise. Animal experiments have shown a period of particular sensitivity shortly after birth.2 Moreover, the heads, ears, and external auditory canals of children are shaped differently from those of adults, allowing greater amplification of high frequency sounds,3 which are relatively more harmful to hearing than low frequency sounds. Over the past decade the incidence of high frequency loss in schoolchildren has not decreased in Scandinavia,4 although it has in protected industrial workers. 1 2

Several studies have reported permanent sensorineural hearing loss in children related to noisy toys, games,5 fire crackers,6 and gunfire …
Elevated Mortality Associated With Armed Conflict—Democratic Republic of Congo, 2002
Authors: Roberts L, Zantop M, Ngoy P, Lubula C, Mweze L
Journal: JAMA (2003)

In August 1998 citing a need to control insecurity on their western borders Rwanda and Uganda sent troops into the Democratic Republic of Congo (DRC) (estimated 2002 population: 51 million). Within 6 months troops from seven neighboring countries were fighting in the DRC with various Congolese groups supporting different invading armies. During 1998-2002 the majority of the fighting occurred in the DRCs five eastern provinces (1996 population: 19.9 million). To assess the impact of the armed conflict on public health the International Rescue Committee (IRC) with sup- port from CDC conducted a nationwide mortality survey to measure DRCs nationwide crude mortality rate (CMR) and to compare CMRs in DRCs five eastern provinces with CMRs in the five western provinces. This report summarizes the results of the survey which indicate that the overall CMR in the DRC is the highest in the world with the majority of deaths caused by preventable infectious diseases. The findings underscore the importance of the ongoing peace process which appears to have contributed to a decrease in mortality rates in eastern DRC and highlights the importance of collecting population-based health data regularly during armed conflicts.  (excerpt)
Abstract 16789: Plasminogen Activator Inhibitor-1 is Predictive of Endothelial Dysfunction Measured as Digital Reactive Hyperemia
Authors: Alanna Morris, Jose Binongo, Joseph Poole, Riyaz Patel, Yusuf Ahmed, Neli Stoyanova, Gary Gibbons, Viola Vaccarino, Rebecca Din-Dzietham, Arshed Quyyumi
Journal: Circulation (2011)

Background: Local hemostasis is regulated by the endothelium, and plasminogen activator inhibitor-1 (PAI-1) acts as the main inhibitor of the fibrinolytic system. Production of PAI-1 is upregulated in chronic inflammatory states such as cardiovascular disease (CVD), and may reflect endothelial dysfunction. Digital reactive hyperemia (RHI) is a convenient test of microvascular and endothelial function. Lower RHI is associated with worse long term outcome. Whether levels of PAI-1 reflect microvascular function measured by RHI has not been studied. Methods: We measured CVD risk factors in 682 participants (mean age 51±9 years, 57% female) enrolled in the Morehouse-Emory Partnership to Eliminate Cardiovascular Health Disparities (META-Health) study. Levels of PAI-1 were examined as continuous, log-transformed values. Digital pulse wave amplitude during reactive hyperemia was assessed using the Endo-PAT 2000 device (Itamar Medical, Israel). Briefly, a reactive hyperemia index (RHI) was calculated as the ratio of baseline to post-hyperemic pulse wave after 5 minutes of forearm cuff inflation. RHI was used as both a continuous and dichotomous variable. Results: Median levels of PAI-1 were 13.3 (IQR 7.2, 26.3) ng/mL. Levels of PAI-1 correlated inversely with the RHI (r=-0.112, p=0.005). Participants with PAI-1 levels in the highest tertile had lower RHI compared to those in the lowest tertile (2.1±0.6 vs. 2.3±0.7, p=0.004). Furthermore, levels of PAI-1 in the highest tertile increased the odds of a RHI &lt;1.35, a value indicative of coronary endothelial dysfunction, by 3.7 (95% CI 1.2, 11.3). After adjustment for age, gender, race, smoking, hypertension, diabetes, waist circumference, mean arterial pressure, glucose, and lipid profile, PAI-1 remained a significant predictor of lower RHI (p=0.02). Conclusion: PAI-1 predicts lower RHI, indicating reduced digital microvascular reactivity that may be due to endothelial dysfunction. Since impaired RHI has been associated with worse long-term outcomes, this may be a useful tool for monitoring risk and following response to therapeutic PAI-1 antagonists
Minocycline for acne
Authors: F P Meyer
Journal: BMJ (1996)

Table 1-Estimated prenatal and postnatal prevalences (per 100 000) of diagnosis of Turner's syndrome karyotype by test method (amniocentesis or chorion villus sampling) and karyotype (45,X and others).Figures in parentheses are 95% confidence intervals Postnatal Prenatal prevalence among Karyotype prevalence untested girls Relative risk Amniocentesis without ultrasonography 45,X 64.6 (42.2 to 94.7) 16.0 (13.1 to 19.3) 4.0 (2.7 to 6.0) Others 84.5 (58.5 to 118.1) 15.6 (12.7 to 18.8) 5.4 (3.9 to 7.7) Total 149.1 (113.8 to 191.6) 31.5 (27.5 to 36.1) 4.7 (3.6 to 6.1) Chorion villus sampling without ultrasonography 45,X 271.2 (165.8 to 418.6) 16.0 (13.1 to 19.3) 17.0 (12.0 to 24.0) Others 40.7 (8.4 to 118.9) 15.6 (12.7 to 18.8) 2.6 (0.9 to 7.9) Total 311.9 (197.8 to 467.7) 31.5 (27.5 to 36.1) 9.9 (7.0 to 14.0)
Abstract 702: BRAF V600E mutation in benign and malignant epithelial odontogenic tumors
Authors: Marina Goncalves Diniz, Carolina Cavalieri Gomes, Bruna Viana Antonini Guimaraes, Alessandra Pires Duarte, Ricardo Santiago Gomez
Journal: Cancer Research (2015)

Abstract The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82%) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83%) unicystic, 7/9 (78%) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36%) malignant tumours, specifically, 3/8 (38%) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E mutation was less frequent in odontogenic carcinomas than in ameloblastomas. In ameloblastomas, this mutation occurred at similar proportions in cases from the mandible and maxilla, as well as among unicystic, multicystic and desmoplastic variants, suggesting that there is no difference in their molecular pathogenesis. Our findings support the possibility for personalised, molecular targeted therapy for ameloblastomas and ameloblastic carcinomas harbouring the BRAFV600E mutation. Supported by: FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais), CNPq (National Council for Scientific and Technological Development) and CAPES (Coordination for Improvement of Higher Education Personnel), Brazil Citation Format: Marina Goncalves Diniz, Carolina Cavalieri Gomes, Bruna Viana Antonini Guimaraes, Alessandra Pires Duarte, Ricardo Santiago Gomez. BRAF V600E mutation in benign and malignant epithelial odontogenic tumors. [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 702. doi:10.1158/1538-7445.AM2015-702
Abstract 2658: Growth Differentiation Factor-15 (GDF-15) and the Risk of Recurrent Events in Patients Stabilized after Acute Coronary Syndrome: Observations from PROVE IT-TIMI 22
Authors: Marc P Bonaca, David A Morrow, Eugene Braunwald, Christopher P Cannon, Wei Guo, Tibor Kempf, Marc S Sabatine, Anja Quint, Lars Wallentin, Kai Wollert
Journal: Circulation (2008)
Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol
Authors: Lloyd T Lam, Oxana K Pickeral, Amy C Peng, Andreas Rosenwald, Elaine M Hurt, Jena M Giltnane, Lauren M Averett, Hong Zhao, R Eric Davis, Mohan Sathyamoorthy, Larry M Wahl, Eric D Harris, Judy A Mikovits, Anne P Monks, Melinda G Hollingshead, Edward A Sausville, Louis M Staudt
Journal: Genome biology (2001)

Flavopiridol, a flavonoid currently in cancer clinical trials, inhibits cyclin-dependent kinases (CDKs) by competitively blocking their ATP-binding pocket. However, the mechanism of action of flavopiridol as an anti-cancer agent has not been fully elucidated.Using DNA microarrays, we found that flavopiridol inhibited gene expression broadly, in contrast to two other CDK inhibitors, roscovitine and 9-nitropaullone. The gene expression profile of flavopiridol closely resembled the profiles of two transcription inhibitors, actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB), suggesting that flavopiridol inhibits transcription globally. We were therefore able to use flavopiridol to measure mRNA turnover rates comprehensively and we found that different functional classes of genes had distinct distributions of mRNA turnover rates. In particular, genes encoding apoptosis regulators frequently had very short half-lives, as did several genes encoding key cell-cycle regulators. Strikingly, genes that were transcriptionally inducible were disproportionately represented in the class of genes with rapid mRNA turnover.The present genomic-scale measurement of mRNA turnover uncovered a regulatory logic that links gene function with mRNA half-life. The observation that transcriptionally inducible genes often have short mRNA half-lives demonstrates that cells have a coordinated strategy to rapidly modulate the mRNA levels of these genes. In addition, the present results suggest that flavopiridol may be more effective against types of cancer that are highly dependent on genes with unstable mRNAs.
Abstract 4485: Clinical, Procedural and Angiographic Predictors of Stent Thrombosis Following Drug-Eluting Stent Implantation in Unselected Patients from the Real-World Clinical Practice with Clinical Follow-up (FU) up to 6 Years
Authors: Ricardo A Costa, Amanda Sousa, Adriana Moreira, J. Ribamar Costa, Galo Maldonado, Manuel Cano, Fausto Feres, Luiz A Mattos, Rodolfo Staico, Alexandre Abizaid, Leopoldo S Piegas, Ricardo Pavanello, Marcos Barbosa, Mariana Carballo, Otávio Berwanger, J. Eduardo Sousa
Journal: Circulation (2008)

DES has demonstrated marked efficacy on reducing restenosis, and therefore TLR, in previous randomized clinical trials compared to bare metal stents. Thus, a widespread use of DES has been observed since their introduction into clinical practice, including treatment of high-risk subgroups. However, recent studies including pts from the “real-world” have raised questions regarding the long-term safety of DES, especially in more complex subsets. Between May/02-Jan/08, 2,365 unselected pts all comers for PCI with DES were prospective enrolled in this single center study. Lesion criteria included ≥1 lesion ≥50% stenosis. Clinical FU was assigned at 1, 6 and 12 months, and yearly up to 6 years (median time: 3.6 yrs). Stent thrombosis (ST) was defined according to the Academic Research Consortium. Overall, 29% of pts had diabetes, 60% multivessel disease, 40% presented with ACS (including 15% AMI). LAD was treated in 43%; 67% of lesions had complex morphology (type B2/C), including 29% mod./severe calcification, 32% eccentric, 5% ostial lesion location, and 5% in-stent restenosis. A total of 3,634 DES were implanted, and 40% had multiple stenting procedure. At late FU (98.3%), overall ST rate was 1.6% (N=38); of that, 61% were definitive (angiographic confirmation), 42% occurred between 1–12 months (late ST), and a fatal event was reported in 47%. By multivariate analysis, ST was associated to: current smoking (HR 2.59; 95%CI 1.18 –5.67; P=0.018), PCI in AMI (HR 3.50; 95%CI 1.31–9.40; P=0.013), multiple steting procedure (HR 1.81; 95%CI 1.09 –3.02; P=0.023), lesion postdilatation (HR 0.50; 95%CI 0.29 – 0.90; P=0.020), eccentric morphology (HR 1.86; 95%CI 1.03–3.34; P=0.039), mod./severe calcium (HR 2.38; 95%CI 1.34 – 4.23; P=0.003), and final residual stenosis by QCA (HR 1.04 per % unit increase; 95%CI 1.01–1.06; P=0.003). In this study, the cumulative incidence of ST up to 6 years clinical FU was very low (1.6%); however, it was associated with a fatal event in half of cases. In this analysis, ST occurred mostly between 1–12 months, and was associated with current smoking, PCI in AMI, multiple stenting, postdilatation, complex lesion morphology including eccentric and significant calcium, and stent underexpansion.
News
Authors: Clare Dyer
Journal: BMJ (1993)

Law lords rule that Tony Bland does not create precedent Tony Bland, the unconscious patient at the centre of Britain's first right to die case, is expected to end his life quietly this month at Airedale Hospital, Keighley, West Yorkshire.In a historic judgment last week, five Law Lords unanimously ruled that doctors caring for the 21 year old victim of the Hillsborough football ground disaster would not be acting unlawfully if they stopped artificially feeding him.The case, one of the most emotive ever to come before the British courts, may lead to legislation to define when and in what way doctors may intervene to end a patient's life.A committee of peers is to examine the area of medical ethics and the criminal law, including the issue of euthanasia.Delivering judgment, two of the five Law Lords made a strong plea for parliament to legislate: to lay down guidelines for future cases and take such decisions out ofthe hands of the courts.In the meantime, the judges said, Tony Bland's case created no precedent, and doctors wanting to discontinue feeding in other cases should first seek a declaration from the court.Their lordships upheld decisions by the president ofthe High Court's family division, Sir Stephen Brown, and three Appeal Court judges that withdrawing artificial nutrition and hydration from Tony Bland, who has been in a persistent vegetative state for nearly four years, would not be unlawful.The ruling opens the way for health authorities to seek similar declarations in other cases.There are thought to be more than 1000 patients in a persistent vegetative, state in Britain.Airedale NHS Trust brought the case with the support of Tony Bland's parents, Allan and Barbara Bland, who wanted their son to be allowed to "die with dignity."The official solicitor, David Venables, representing Tony Bland, appealed to the House of Lords to ensure a definitive ruling on the issue from Britain's highest court.Giving judgment, Lord Keith said that a doctor was under no duty to continue to treat a patient when a large body of informed and responsible medical opinion was to the effect that no benefit would be conferred by con- tinung.It did no violence to the principle of the sanctity of life to hold that it was lawful to cease giving medical treatment to a patient who had been in a persistent vegetative state for three years, considering that treatment involved manipulation of the patient's body without his consent Iand conferred no benefit on him.
Atlas of Electroencephalography
Authors: Frederic Andrews Gibbs, Erna L. Gibbs
Journal: JAMA (1941)

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
Clinical predictors for long-term benefit of cetuximab maintenance therapy – Single center subanalysis of the GEMTAX IV trial
Authors: Stefan Rüdiger, Cornelia Kropf, Gerald Schmid-Bindert, Thomas Wibmer, Martin Lanzinger, Kathrin Stoiber, Joanna Blanta, Wolfgang Rottbauer, Christian Schumann
Journal: European Respiratory Journal (2011)

The Gemtax IV trial compares a platinum-containing doublet (Arm B) vs. a platinum-free sequential chemotherapy with docetaxel and gemcitabine (Arm A), both arms in combination of cetuximab until progression. Our center included 59 patients in the GEMTAX IV trial so far. From them 9 patients received cetuximab for 10 or more cycles. We analyzed clinical markers in relation to long term therapeutic benefit from cetuximab.  A median of 13 cycles (10-15) with cetuximab was administered; mean age was 63 years (53-75). The relations of male to female, non-squamous to squamous histology, and treatment regimen Arm A to Arm B were 2:1 respectively. The median progression free survival was 10 months (8-13) and overall survival 22 months (9-33) so far. Seven of 9 patients developed an acne-like rash within 5 weeks of cetuximab treatment. Eight of 9 patients were former or current heavy smoker.  Patients with long-term benefit from cetuximab maintenance after induction chemotherapy were mostly male, former or current smoker, of non-squamous histology and presented rash early. In accordance with data from the FLEX trial, to monitor rash could be helpful on idenzifying patients who could benefit from cetuximab mainentance therapy.
Controversies in management: Denying access would do more harm than good
Authors: P H Smee
Journal: BMJ (1996)

At one level this debate is as old as insurance itself. The principle of insurance is that individuals bring a risk that is then pooled among a large number of people who wish to make provision against the same risk. The same principle applies to life insurance; even though we all have to die, none of us knows when this will happen but some are more clearly at risk from a premature death than others. This has to be reflected in the premium. A life insurance company has to evaluate what risk each person brings to the pool as accurately as possible. Otherwise some people will have paid sums that do not reflect their risk and will be unfairly advantaged; this can be only at the expense of other policy holders.

Insurance companies do not have a limitless pot of gold from which claims are paid. Their funds represent the money put in by policy holders, and if some do not declare information that would allow an accurate evaluation of their risk then they will profit at other customers' expense. Any …