tbuckley/cabot-search huggingface dataset:
Changes in the US Medical Licensure Examination and Impact on US Medical Schools
Authors: Steven A. Wartman, John H. Littlefield
Journal: JAMA (2005)

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
Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults
Authors: Pranav S. Garimella, Mary L. Biggs, Ronit Katz, Joachim H. Ix, Michael R. Bennett, Prasad Devarajan, Bryan R. Kestenbaum, David S. Siscovick, Majken K. Jensen, Michael G. Shlipak, Paulo H.M. Chaves, Mark J. Sarnak
Journal: Kidney International (2015)
Sirolimus-Eluting Versus Paclitaxel-Eluting Stent Implantation for the Percutaneous Treatment of Left Main Coronary Artery Disease
Authors: Marco Valgimigli, Patrizia Malagutti, Jiro Aoki, Héctor M. Garcia-Garcia, Gaston A. Rodriguez Granillo, Carlos A.G. van Mieghem, Jurgen M. Ligthart, Andrew T.L. Ong, George Sianos, Evelyn Regar, Ron T. Van Domburg, Pim De Feyter, Peter de Jaegere, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2006)
Targeting PI3Kδ: Emerging Therapy for Chronic Lymphocytic Leukemia and Beyond
Authors: Manman Wei, Xiang Wang, Zilan Song, Mingkun Jiao, Jian Ding, Ling-Hua Meng, Ao Zhang
Journal: Medicinal Research Reviews (2015)

Chronic lymphocytic leukemia (CLL) remains the most incurable leukemia. Early chemotherapeutic treatments, including alkylating agents, purine nucleoside derivatives, and immunotherapeutic antibodies, only show limited benefits for patients but severe off-target related side effects. Recent advances in understanding of the critical molecular pathways of regulating proliferation and survival of B-CLL cells have spurred a new therapeutical strategy by selectively targeting phosphoinositide 3-kinase delta (PI3Kδ). Idelalisib, a first-in-class PI3Kδ-selective small molecule has received the FDA's fast-track approval in July of 2014 as a new treatment of CLL, indolent B-cell non-Hodgkin's lymphoma, and relapsed small lymphocytic lymphoma. Undoubtedly, the success of idelalisib has provided a solid support in the development of PI3Kδ-specific inhibitors and reformed the concept of treating CLL. However, the number of reported selective inhibitors of PI3Kδ is very limited and very few have advanced into clinical trials. The mechanism of their actions remains elusive. More profound understanding on the modes of action of new PI3Kδ inhibitors will further validate the PI3Kδ-targeting strategy, and help to identify biomarkers capable of stratifying patients who will most likely benefit from the therapy.
Long Noncoding RNA Related to Cartilage Injury Promotes Chondrocyte Extracellular Matrix Degradation in Osteoarthritis
Authors: Qiang Liu, Xin Zhang, Linghui Dai, Xiaoqing Hu, Jingxian Zhu, La Li, Chunyan Zhou, Yingfang Ao
Journal: Arthritis & Rheumatology (2013)

Long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biologic processes, but knowledge of lncRNAs in osteoarthritis (OA) is limited. The aim of this study was to identify lncRNA expression in articular cartilage and to explore the function of cartilage injury-related lncRNAs (lncRNA-CIR) in OA.To identify lncRNAs specifically expressed in OA cartilage, we compared the expression of lncRNAs in OA cartilage with that in normal cartilage using microarray and quantitative polymerase chain reaction (qPCR) analyses. In OA cartilage, lncRNA-CIR was specifically, differentially, and highly expressed. The function of lncRNA-CIR was determined by silencing and overexpression in vitro. Extracellular matrix (ECM)-related molecules were detected by qPCR, Western blot, and immunofluorescence analyses.Up to 152 lncRNAs were found to be differentially expressed (>8-fold) in OA and normal cartilage (82 lncRNAs more highly expressed and 70 less highly expressed in OA cartilage than in normal cartilage). A specific differentially expressed lncRNA-CIR was selected according to the results of the higher expression in OA cartilage and OA chondrocytes. The expression of lncRNA-CIR increased in chondrocytes with in vitro treatment with interleukin-1β and tumor necrosis factor α. Silencing of lncRNA-CIR by small interfering RNA promoted the formation of collagen and aggrecan and reduced the expression of matrix-degrading enzymes, such as MMP13 and ADAMTS5. The expression of collagen and aggrecan was reduced, whereas the expression of matrix-degrading enzymes was increased, after overexpression of lncRNA-CIR.The results indicate that lncRNA-CIR contributes to ECM degradation and plays a key role in the pathogenesis of OA. We propose that lncRNA-CIR could be used as a potential target in OA therapy.
Bereavement in adult life
Authors: D. Mazza
Journal: BMJ (1998)

Prognosis of symptoms that are medically unexplained Every neurology service should have access to specialist liaison psychiatryEditor-Crimlisk et al's report on the outcome of motor symptoms that were medically unexplained in a cohort first identified at the National Hospital for Nervous Diseases is welcomed by those interested in the psychiatry of physical illness. 1 Slater's work, based on cohorts recruited in the 1950s, overestimated the likelihood of misdiagnosis in modern neurology, 2 and his conclusions have dissuaded psychiatrists from becoming involved in the management of hysteria.O'Brien's editorial on Crimlisk et al's study could have sounded two cautionary notes. 3Firstly, the study was not based on a true inception cohort, and it was recruited from a highly specialised centre.Usually, these factors lead to the finding of a worse prognosis than if only incident cases were included and the sample was less prone to recruitment bias.In this case, however, the bias may have been in the other direction.Patients seen at the National Hospital are likely to have been more exhaustively investigated and observed for longer (either in this episode or before referral) than they would be in most hospitals, so that the chances of misdiagnosis are reduced.We should not generalise the study findings to hospitals where initial assessment may be undertaken with little or no access to specialist neurological opinion or investigations.Secondly, the negative message-that high rates of undetected neurological disease are not seen at follow up-has been allowed to obscure the important positive findings of the study.Even years later, the patients had disabling physical symptoms and substantial psychiatric problems.As in Slater's original study, preventable deaths occurred from suicide and the complications of immobility.Many people were apparently not referred for psychiatric help either at the time of the initial presentation or subsequently.The important conclusion of Crimlisk et al's study must be that every neurology service should have easy access to referral to specialist liaison psychiatry. 4This group of patients, who are difficult to treat, are often resistant to treatment, and have a poor prognosis, may then have a reasonable chance of obtaining appropriate treatment for their primary disorder.
Jury finds drug 80% responsible for killings
Authors: Deborah Josefson
Journal: BMJ (2001)

A US jury in Wyoming has found the British based pharmaceutical company GlaxoSmithKline responsible for a spate of family murders and a suicide committed by a patient taking the antidepressant paroxetine, which is marketed as Paxil in the United States and Seroxat in the United Kingdom.

The jury awarded $6.4m (£4.6m) to the surviving family of Donald Schell, a 60 year old man who killed his wife, daughter, and granddaughter before killing himself.

Mr Schell reportedly suffered from episodic depression but had not expressed suicidal or homicidal ideation or violent behaviour before being prescribed paroxetine, an antidepressant of the selective serotonin reuptake inhibitor class. Several years earlier he had been prescribed fluoxetine (Prozac), a related drug, but he was taken off that because he became extremely agitated.

In February …
Suramin: rapid loading and weekly maintenance regimens for cancer patients.
Authors: R E van Rijswijk, A C van Loenen, J Wagstaff, E Meijer, R Lopez, C J van Groeningen, J J Heimans, H M Pinedo
Journal: Journal of Clinical Oncology (1992)

Suramin is an anticancer agent with a narrow therapeutic window and a terminal half-life of 45 to 55 days. These characteristics make it necessary to control accurately the serum concentrations of the drug. Therefore, the aim of the present study was to develop a rapid loading regimen, followed by weekly administration of suramin to maintain serum concentrations of between 150 and 300 micrograms/mL for 8 weeks.Eligible patients were treated with five different loading regimens. Initially, weekly maintenance doses were estimated manually by the treating physician. Subsequently, computer-assisted dosing that used Bayesian pharmacokinetic modeling was used.Thirty-eight courses of suramin that were administered to 35 patients were studied. The optimal loading regimen consisted of a continuous infusion of 600 mg/m2 during a 24-hour period, which resulted in a mean serum concentration of 319 micrograms/mL. Potentially toxic concentrations that were observed with shorter infusions were avoided. Maintenance treatment, which used the weekly administration of suramin during a 6-hour period, seemed to be able to maintain mean suramin serum trough concentrations of 150 micrograms/mL, while preventing mean peak concentrations of more than 300 micrograms/mL. The use of Bayesian pharmacokinetics was superior to manual estimation in tailoring the optimal dose to the therapeutic window.Continuous infusion is the optimal way of delivering suramin during the loading phase. To maintain trough levels and peak levels within a narrower therapeutic window, suramin will have to be administered more frequently than once a week. Bayesian modeling based on individual serum levels and population pharmacokinetics allows accurate dosing to maintain suramin levels within the therapeutic window.
Breast self examination may do more harm than good.
Authors: David Spurgeon
Journal: BMJ (2001)

Physicians should no longer routinely teach women aged 40-69 breast self examination as a screening technique for cancer because it can do more harm than good, the Canadian Task Force on Preventive Health Care has announced. The task force counsels healthcare providers on effective screening methods.

In a systematic analysis of 34 years of published studies of breast self examination, the Canadian task force concluded that there was evidence that the technique had no benefits and good evidence that harm is done (Canadian Medical Association Journal 2001;164:1837-46).

Dr …
Abstract 429: HERP2 as a novel molecular marker and therapeutic target in glioblastoma
Authors: Kiran Kumar Velpula, Swapna Asuthkar, William Lee, Andrew J. Tsung
Journal: Cancer Research (2014)

Abstract Glioblastoma (GBM) remains one of the most lethal and difficult-to-treat cancers of the central nervous system despite a multi-modality approach. The poor prognosis in GBM patients is due to therapeutic resistance which calls for identifying novel molecular therapeutic targets. Recently, HES-related repressor protein 2 (HEPR2), a mediator of notch signaling has been identified as a molecular target implicated in chemoresistance. This current study aims at both the epigenetic and transcription factor regulation as the potential mechanisms resulting in the expression of HES-related repressor protein 2 (HERP2) in GBM patient specimens and cell lines. Using immunohistochemistry and immunoblot analysis, we observed that the HERP2 protein is highly expressed in human GBM tissues and glioma cells (4910, U251 and 5310) and is significantly correlated with O6-alkylguanine DNA alkyltransferase (MGMT) levels. We also observed that the expression of HERP2 was dependent on the methylation status of a HERP2 promoter-associated CpG island region as evidenced by prominent PCR products using methylation-specific PCR (MSP) analysis. Interestingly, treatment of GBM cells with demethylating agent, 5-aza-2’-deoxycytidine resulted in hypomethylation, whereas sodium butyrate-treated cells remained specific for methylated CpG islands. Additionally, we also demonstrated a positive regulatory loop between HERP2 and NOTCH1 using rescue experiments. Further, we show the anti-tumorigenic role of siHERP2 to be mediated by the negative regulation of NOTCH1 protein. Our studies indicate that targeting HERP2 in cancer patients undergoing chemotherapy will have favorable therapeutic implications. Citation Format: Kiran Kumar Velpula, Swapna Asuthkar, William Lee, Andrew J. Tsung. HERP2 as a novel molecular marker and therapeutic target in glioblastoma. [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 429. doi:10.1158/1538-7445.AM2014-429
The Heart in Hyperthyroidism
Authors: Henry M. Thomas
Journal: Annals of Internal Medicine (1931)

ExcerptIn discussing the heart in hyperthyroidism I shall try to take up clinical points about which there has been much controversy in the past. In order to establish a proper background I shall briefly summarize the history of this subject.In the first allusion to hyperthyroidism made by Parry1in 1786 (and published posthumously in 1825) eight cases of a peculiar heart disease, attended by exophthalmos and thyroid enlargement were described. He evidently considered the disease primarily a cardiac affection with secondary exophthalmos and enlargement of the thyroid gland. Although Adleman2in 1829 spoke of "Kropfherz," the Englishmen, Graves,3Stokes,4...
Smooth muscle cells as immunological relay in acute pulmonary inflammation by ADAM17-mediated ErB receptor transactivation
Authors: Daniela Dreymueller, Christian Martin, Julian Schumacher, Esther Groth, Julia Katharina Boehm, Kathleen Reiss, Stefan Uhlig, Andreas Ludwig
Journal: European Respiratory Journal (2013)

Acute respiratory distress syndrome (ARDS) can develop from acute pulmonary inflammation caused by pathogen infection or acid aspiration. Danger signals of the stimulated epithelium have to be relayed to vascular responses at the endothelial layer, eventually by smooth muscle cell mediator release. This release may be regulated by the action of the disintegrin and metalloproteinase (ADAM) 17. In vivo, we compared Adam17+/+ and Tagln-Adam17-/- (deficient for SMC-ADAM17) for LPS- or acid-aspiration-induced pulmonary inflammation. In vitro, primary murine and human tracheal SMC were analyzed for cytokine release and the mediating signaling pathways targeting ADAM17 and pathway members by pharmacological and transcriptional inhibition. The in vivo-conditions were mimicked by either LPS stimulation or treatment with acid-treated epithelial cell (BEAS-2B) supernatant. The importance of these ADAM17-dependent signaling pathways in vivo was demonstrated by instillation of TNFα, CXCL1, or coinstillation of LPS and TGFα into the lungs. SMC-ADAM17 acts proinflammatory in both in vivo-models, demonstrated by the reduction of cytokine and neutrophil attracting chemokine release, leukocyte recruitment, and edema formation in Tagln-Adam17-/- in comparison to Adam17+/+ mice. Endotoxin-induced inflammation is mediated by ADAM17-dependent ErbB1 transactivation via TGFα and release of TNFα and CXCL1 by SMC, whereas acid-induced inflammation is relayed by ErbB4 activation via neuregulins. Thus, local targeting of ADAM17 and/or the transactivation pathways in SMC may be an option for the development of an efficient therapy for acute pulmonary inflammation.
Ibrutinib rash in a patient with 17p del chronic lymphocytic leukemia
Authors: Gabriel Mannis, Davina Wu, Tiffany Dea, Theodora Mauro, Gerald Hsu
Journal: American Journal of Hematology (2014)

A 67-year-old man with chronic lymphocytic leukemia (CLL) and deletion of chromosome 17p presented to clinic for evaluation of leukocytosis (total white blood cell count 149,000/mm3, absolute lymphocyte count 144,000/mm3) associated with fatigue, drenching night sweats, and recurrent viral infections. He had been treated previously with a combination of rituximab, cyclophosphamide, vincristine, and prednisone as well as rituximab and bendamustine (B-R), with the most recent therapy 3 years prior to his clinic visit. He had previously declined referral for hematopoietic stem cell evaluation. He was started on ibrutinib 420 mg PO daily in combination with allopurinol 300 mg PO daily for prophylaxis against tumor lysis syndrome. Two weeks after beginning therapy, he developed a painless, non-pruritic, rash that began on his wrists and then spread to his entire body (Image 1). The rash was characterized by a diffuse distribution of bright red edematous papules, ranging from 0.5 to 1 cm in diameter, with sparing of his palms and soles. He was evaluated in the Emergency Department and both allopurinol and ibrutinib were held. His absolute eosinophil count at the time was within the normal range (100/mm3). Within several days his rash had completely resolved, and given consideration for allopurinol as the etiology of his rash, he was restarted on dose-reduced ibrutinib (140 mg PO daily) without allopurinol. After a single dose, he developed recrudescence of his full-body rash and ibrutinib was once again discontinued. The rash again resolved within several days of discontinuing ibrutinib. Ibrutinib (Imbruvica, Pharmacyclics/Janssen Biotech), an oral Bruton's tyrosine kinase inhibitor, was approved in February 2014 by the Federal Drug Administration for the treatment of CLL patients who have received at least one prior therapy. Ibrutinib is generally very well-tolerated, with few Grade 3 or higher adverse events 1-3. In published studies, rash occurs at a frequency of 15–27%, although no identifying characteristics have been reported. In this case, clinical features distinguishing the rash from a classic allopurinol-mediated rash included its presentation with edematous papules (versus the morbilliform rash commonly associated with allopurinol) and its peripheral-to-central pattern of spread. Painless, non-pruritic edematous papules on the trunk of a patient who developed an ibrutinib-related rash. Lesions began on the wrists and arms and subsequently generalized to the entire body.
The European Genome-phenome Archive of human data consented for biomedical research
Authors: Ilkka Lappalainen, Jeff Almeida-King, Vasudev Kumanduri, Alexander Senf, John Dylan Spalding, Saif ur-Rehman, Gary Saunders, Jag Kandasamy, Mario Caccamo, Rasko Leinonen, Brendan Vaughan, Thomas Laurent, Francis Rowland, Pablo Marin-Garcia, Jonathan Barker, Petteri Jokinen, Angel Carreño Torres, Jordi Rambla de Argila, Oscar Martinez Llobet, Ignacio Medina, Marc Sitges Puy, Mario Alberich, Sabela de la Torre, Arcadi Navarro, Justin Paschall, Paul Flicek
Journal: Nature Genetics (2015)

Paul Flicek and colleagues provide an update on the European Genome-phenome Archive (EGA), a service of the European Bioinformatics Institute (EMBL-EBI) and the Center for Genome Regulation (CRG). The authors describe the EGA policies and infrastructure, how access decisions are made, methods for data submission and future plans for expansion of this database. The European Genome-phenome Archive (EGA) is a permanent archive that promotes the distribution and sharing of genetic and phenotypic data consented for specific approved uses but not fully open, public distribution. The EGA follows strict protocols for information management, data storage, security and dissemination. Authorized access to the data is managed in partnership with the data-providing organizations. The EGA includes major reference data collections for human genetics research.
Abstract 3727: Drug screen on six co-cultured GBM cell lines using a multiplex luciferase assay
Authors: Sjoerd van Rijn, Lotte Hiddingh, Thomas Wurdinger, Ravi Narayan
Journal: Cancer Research (2014)

Abstract Despite the addition of temozolomide (TMZ) to the glioblastoma (GBM) treatment regimen, disease outcome is still poor and additional therapeutic options are necessary. One major obstacle in the GBM treatment is TMZ resistance of the tumor cells resulting in relapse of the disease with no alternative treatments known. In an effort to discover additional treatment modalities we are performing drug screens on GBM cell lines, using wild-type variants and acquired TMZ resistant variants of these cell lines. To be able to screen a range of different cells, we adapted a multiplex bioluminescence reporter assay developed in our lab. This bioluminescent reporter assay is based on the Gaussia luciferase (Gluc) fused to an epitope tag. Different cell lines can be equipped with Gluc fused to different epitope tags (Gluc-tag) so that each cell lines expresses Gluc and a cell line specific epitope tag. Antibody immunoprecipitation allows us to separate the different Gluc-tags and quantify the relative activities of the different cell lines. Activity of each specific Gluc-tag represents the relative number of a specific cell line in the mixed population. Since Gaussia luciferase and the epitope tag is secreted by the cells, we can detect the cell line specific reporters ex vivo in the culture medium or animal blood. Using this novel method in a drug screen we aim to identify additional subtype specific therapy strategies for GBM braintumors. Citation Format: Sjoerd van Rijn, Lotte Hiddingh, Thomas Wurdinger, Ravi Narayan. Drug screen on six co-cultured GBM cell lines using a multiplex luciferase assay. [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 3727. doi:10.1158/1538-7445.AM2014-3727
Foot Disorders. Medical and Surgical Management.
Authors: Nicholas J. Giannestras
Journal: Annals of Internal Medicine (1967)

myocardial infarction could have been longer. Although Dr. Owen hails from across the Atlantic at Newcastle upon Tyne, terminology is fully acceptable for American students. The printing is good, and the electrocardiograms are clearly presented and reproduced. This excellent programmed text is highly recommended to many audiences. Medical students will be delighted by the way Dr. Owen has developed a more meaningful approach to electrocardiography. Because of the present emphasis on coronary care units and the in¬ creasing need for nurses trained in electrocardiography, this text should be utilized in postgraduate nurses' coronary training programs. Au¬ thors who wish to develop other programmed texts will find this one difficult to emulate. The author is