tbuckley/cabot-search huggingface dataset:
Mantle cell lymphoma: 2017 update on diagnosis, risk‐stratification, and clinical management
Authors: Julie M. Vose
Journal: American Journal of Hematology (2017)

Abstract Disease Overview Mantle cell lymphoma (MCL) is a non‐Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4‐5 years. Diagnosis Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX‐11 or a low Ki‐67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma. Risk Stratification The MCL International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki‐67 proliferative index if available. The median OS for the low‐risk group was not reached (5‐year OS of 60%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group. Risk‐Adapted Therapy For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytotoxic Regimen followed by autologous stem cell transplantation should be considered. Rituximab maintenance after autologous stem cell transplantation has also improved the progression‐free and overall survival. For older symptomatic MCL patients with intermediate or high risk MIPI, combination chemotherapy with R‐CHOP, R‐Bendamustine, or a clinical trial should be considered. In addition, rituximab maintenance therapy may prolong the progression‐free survival. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), lenalidamide (anti‐angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase [BTK] inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Clinical trials with novel agents are always a consideration for MCL patients.
A Phase II study of gefitinib combined with docetaxel as first-line treatment in patients with advanced breast cance
Authors: F. Ciardiello, T. Troiani, F. Caputo, M. De Laurentiis, G. Palmieri, A. Marinelli, G. Colantuoni, M. R. Diadema, S. De Placido, A. R. Bianco
Journal: Journal of Clinical Oncology (2004)

725 Background: The orally active EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ('Iressa', ZD1839) has antitumor activity and additive or synergistic activity when combined with docetaxel in preclinical models (Clin Cancer Res 2000; 6: 2053–63). This Phase II study investigated gefitinib and docetaxel as first-line combination therapy in patients with metastatic breast cancer. Methods: Fourteen patients received gefitinib (250 mg/day orally) and docetaxel (75 mg/m2 iv) on Day 1 every 3 weeks. If there was no unacceptable toxicity, up to 28 additional patients would receive gefitinib and docetaxel (100 mg/m2 iv). After 6 cycles, patients would continue on gefitinib monotherapy until disease progression or unacceptable toxicity. RECIST and Kaplan-Meier analyses were used to evaluate response or median duration of response and time to progression, respectively. Results: From August 2002 to November 2003, 28 patients were enrolled (14 at each docetaxel dose) and evaluated for toxicity. Combination therapy was well tolerated, with no major differences between docetaxel doses. Grade 3 and 4 adverse events were neutropenia in 21% and 36% of patients, respectively (including 1 patient with febrile neutropenia), grade 3 anemia (1) and diarrhea (2), and grade 4 skin rash (1). All 14 patients treated with docetaxel 75 mg/m2 were evaluable for response. The response rate was 64% (95% CI: 34–87%): 2 complete responses (CR); 7 partial responses (PR). The disease control rate was 86% (95% CI: 57–98%). Median duration of response and time to progression were 5.5 and 7.6 months, respectively. Ten patients continued to receive gefitinib 250 mg/day monotherapy (median 16 weeks; range 6->30 weeks): 2 patients with PR received monotherapy for >18 weeks and 1 patient with CR received treatment for >30 weeks. Conclusions: In patients with metastatic breast cancer, first-line gefitinib and docetaxel combination therapy was well tolerated and has promising antitumor activity. Further trials are warranted to fully evaluate use in the clinic. 'Iressa' is a trademark of the AstraZeneca group of companies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Getting geared up for the Winter Olympics
Authors: P. Gunby
Journal: JAMA (1979)

Exactly six months from now—at 9:54 AM Sunday, Feb 24—the XIII Winter Games of the 1980 Olympics are scheduled to close in the Adirondack mountain village of Lake Placid, NY. The closing ceremony will evoke differing emotions. Among these, if meticulous preparations have paid off, will be a long sigh of relief from physicians and other health professionals charged with planning and providing medical services to the more than 100,000 athletes, officials, and spectators expected to be present daily for the Feb 13 to 24 events. "We have to hope for the best and plan for the worst," says George G. Hart, MD, a Lake Placid-born family practitioner who is chairman of medical arrangements for the Olympic Organizing Committee. Hart, who has practiced in the community since shortly after flight surgeon service in World War II, says that as far as the winter sports themselves are concerned, downhill high-speed skiing
Social Medicine
Journal: JAMA (1926)

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
Phthalate Ester Residues: Their Metabolism and Analysis in Fish
Authors: David L. Stalling, James W. Hogan, James L. Johnson
Journal: Environmental Health Perspectives (1973)

During the course of our analysis of fish and other aquatic materials for pesticide residues, unknown components were often detected.Concern about the identity of late eluting gas-liquid chromatographic (GLC) peaks in fish and water extracts led to the identification of phthalic acid esters (PAEs) as environmental contaminants (1).Further study of these contaminants with a GLC-mass spectrometer (GLC-MS) led to their identification as di-2-ethylhexyl phtha- late (DEHP) and di-n-butyl phthalate (DBP).Preliminary data from acute toxicity tests indicate that these compounds are relatively low in toxicity.Chronic studies, however, indicate that they may have more subtle effects on reproduction of some aquatic species (2).Residue data obtained from a variety of areas, dietary materials, and samples related to fish rearing operations have established some information on the incidence of PAEs in relation to pesticides and polychlorinated biphenyl contaminants (Table 1).PAE residues in water appeared to be correlated with rivers draining industrialized or heavily popu- lated areas (John Hesse, Michigan Depart- ment of Natural Resources, East Lansing, Michigan 1972 personal communication).However, the distribution of PAEs in the aquatic environment remains to be defined.PAEs are commonly used as plasticizers, especially in poly(vinyl chloride) plastics.In
THE USE OF MENTHOL IN PRURITUS.
Journal: JAMA (1891)

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
Asymmetrical nonocclusive ischemia of the lower extremities
Authors: H. Dardik
Journal: JAMA (1974)

Nonocclusive ischemia of the lower extremities may be mistakenly diagnosed as thrombotic or embolic arterial occlusion. This is particularly true when there is asymmetrical involvement of the extremities. Doppler ultrasound flowmeter recordings may be helpful in suggesting the diagnosis, but arteriography is essential for the differentiation between occlusive and nonocclusive states. By confirming arterial patency, needless and often hazardous surgery can be avoided.
Pictorial Atlas of Skin Diseases and Syphilitic Affections, in Photolithochromes from the models in the museum of the Saint Louis Hospital, Paris. Ernest Beurier, A. Fournier, Tennyson, Hallopeau, Du Castel, physicians to Saint Louis Hospital, Paris, with the co operation of the Honorable Henri Feulard, Curator of the Museum and L. Jacquet, former House Physician.
Journal: JAMA (1897)

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124. Therapeutic Correction of an LCA-Causing Splice Defect in the CEP290 Gene by CRISPR/Cas-Mediated Gene Editing
Authors: Morgan L. Maeder, Rina Mepani, Sebastian Gloskowski, Maxwell Skor, McKensie Collins, Shen Shen, Gregory Gotta, Eugenio Marco, Luis Barrera, Hari Jayaram, David Bumcrot
Journal: Molecular Therapy (2016)

Leber congenital amaurosis (LCA) comprises a genetically heterogeneous group of early-onset retinal disorders characterized by severe loss of vision in the first years of life. Approximately 20% of LCA patients harbor mutations in the CEP290 gene, which exceeds the packaging limit of AAV and is therefore not amenable to traditional gene therapy. Here, we demonstrate a gene editing approach in which the CRISPR/Cas9 system is used to modify the endogenous CEP290 locus and restore normal function of the gene. The most common mutation in CEP290 is the IVS26 c. 2991+1655 AtoG mutation. This point mutation in intron 26 of the gene generates a novel splice donor, resulting in aberrant splicing and the presence of a premature stop codon. Using the S. aureus CRISPR/Cas9 system, we employed a dual-cut approach in which two gRNAs are used to excise the mutation-containing region in primary fibroblasts derived LCA10 patients. Upon gene editing, these cells show correction of the splicing defect as evidenced by a two-fold increase in expression of wildtype CEP290 transcript and a concomitant two-fold decrease in levels of the mutant RNA species. Additionally, Western blotting shows increased expression levels of full-length CEP290 protein. Using targeted amplicon sequencing of computationally predicted sites, as well as the minimally biased GUIDE-Seq method, we have performed broad specificity profiling, allowing us to narrow down the list of top gRNA candidates. The use of the S. aureus CRISPR/Cas9 system enables efficient packaging of the Cas9 gene, as well as two gRNA genes, into a single AAV vector and provides a method for therapeutic delivery of this system into patient photoreceptors.
The Rise of Litigation in Human Subjects Research
Authors: Harvey Murff
Journal: Annals of Internal Medicine (2004)

Letters20 April 2004The Rise of Litigation in Human Subjects ResearchHarvey Murff, MD, MPHHarvey Murff, MD, MPHFrom Vanderbilt University, Nashville, TN 37232.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-8-200404200-00033 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Concerns about litigation associated with clinical trials are becoming increasingly apparent. Examples of “defensive medicine” have already begun to permeate the scientific and ethical reviews of protocols; statements such as “How would it look if a serious adverse event occurred?” or “How would you defend this to the lawyer?” are becoming common. Asking these questions, however, is not necessarily problematic and often results in the critical evaluation of a protocol's safety plan. My concern is not that these questions are asked but rather who will ultimately ask them.Mello and colleagues (1) stated that one significant disadvantage ...References1. Mello MM, Studdert DM, Brennan TA. The rise of litigation in human subjects research. Ann Intern Med. 2003;139:40-5. [PMID: 12834317] LinkGoogle Scholar2. Institute of Medicine.. Responsible Research: A Systems Approach to Protecting Research Participants. Washington, DC: National Academies Pr; 2003. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Vanderbilt University, Nashville, TN 37232. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Rise of Litigation in Human Subjects Research Michelle M. Mello , David M. Studdert , and Troyen A. Brennan The Rise of Litigation in Human Subjects Research Larry D. Scott Metrics 20 April 2004Volume 140, Issue 8Page: 670KeywordsClinical trialsInstitutional review boardsRisk managementSafetySerious adverse events ePublished: 20 April 2004 Issue Published: 20 April 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Longitudinal circulating tumour DNA (ctDNA) monitoring for early detection of disease progression and resistance in advanced NSCLC in FLAURA
Authors: T. Reungwetwattana, J. Gray, A. Markovets, N. Nogami, J.S. Lee, B.C. Cho, B. Chewaskulyong, M. Majem, N. Peled, K. Vishwanathan, A. Todd, Y. Rukazenkov, M. Johnson, C. Barrett, J. Chmielecki, R. Hartmaier, S. Ramalingam
Journal: Annals of Oncology (2019)
Small-bowel endoscopy
Authors: K. Mönkemüller, C. Olano, L. Fry, L. Ulbricht
Journal: Endoscopy (2009)

Modern small-bowel endoscopy is performed using capsule endoscopy and balloon-assisted enteroscopy. Recently, spiral enteroscopy was added to the armamentarium of deep small-bowel endoscopy. As seen from the number of abstracts presented at this year’s Digestive Disease Week (DDW) 2009, there is ongoing clinical and research interest in the field of small-bowel endoscopy, with 130 scientific contributions this year.
DEPARTMENT OF ERROR
Authors: Philip Wilcox, Gino Fornaciari, Francesco Mallegni, Pietro De Leo, Kantorowicz Friedrich, Helmut Vormals, Georg Bondi, Abulafia Frederick
Journal: The Lancet (1999)

patients, and can also contact our hospital information services.Muramoto seems concerned with Jehovah's Witnesses' theology, but his comments do little to advance effective non-blood medical management or to enhance respect for individual autonomy.
A phase I study of the androgen signaling inhibitor ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Dana E. Rathkopf, Michael J. Morris, Daniel Costin Danila, Susan F. Slovin, Jill Elise Steinbrecher, Gabrielle Arauz, Tracy Curley, Peter J. Rix, Edna Chow Maneval, Isan Chen, Martin Fleisher, Jonathan Landa, Josef J. Fox, Steven M. Larson, Howard I. Scher
Journal: Journal of Clinical Oncology (2012)

4548 Background: ARN-509 is a novel small molecule AR antagonist that impairs AR nuclear translocation and binding to DNA, inhibiting tumor growth and promoting apoptosis, with no partial agonist activity. (Clegg et al., 2012) We conducted a phase I trial to assess safety, pharmacokinetics (PK), and determine the recommended phase II dose (RP2D). Methods: Eligible patients with mCRPC received ARN-509 orally on a continuous daily dosing schedule. Seven doses (30, 60, 90, 120, 180, 240, and 300 mg) were tested using standard 3x3 dose escalation criteria. Once drug concentrations were achieved that met or exceeded optimal levels predicted preclinically, an additional 2 dose levels were tested to further confirm the safety margin of ARN-509 (390 and 480 mg). Anti-tumor activity was assessed by PSA, radiographic responses, and FDHT-PET imaging. Results: Thirty patients were enrolled. The most common grades 1-2 treatment-related adverse events were fatigue (38%), nausea (29%), and pain (24%). There was only 1 treatment-related grade 3 adverse event (abdominal pain) at 300 mg, possibly related to a higher pill burden. PK was shown to be linear and dose-dependent. At 12 weeks, 42% of patients have had ≥ 50% PSA declines. Eleven (37%) patients have discontinued the study due to progression, with the longest patient still on study for more than 16 months. FDHT-PET imaging demonstrated AR blockade at 4 weeks across multiple dose levels. Conclusions: In this phase I study, ARN-509 was shown to be safe and well tolerated with linear PK. Based on promising activity across all dose levels and pharmacodynamic evidence of AR antagonism, an optimal biologic dose of 240 mg daily was selected for phase II investigation. DOD/PCF PCCTC trial sponsored by Aragon Pharmaceuticals.
TRTH-23. FEASIBILITY AND SAFETY OF SURGICAL BIOPSY FOR PATIENTS WITH DIPG: PRELIMINARY RESULTS FROM DIPG-BATS
Authors: Nalin Gupta, Liliana Goumnerova, Kanya Ayyanar, William Gump, Anne Bendel, Mahmoud Nagib, Daniel Bowers, Bradley Weprin, Amy-Lee Bredlau, Sri Gururangan, Herbert Fuchs, Ken Cohen, George Jallo, Katie Dorris, Michael Handler, Melanie Comito, Mark Dias, Jason Fangusaro, Stewart Goldman, Tadanori Tomita, Tord Alden, Arthur DiPatri, Sharon Gardner, Matthias Karajannis, David Harter, Karen Gauvain, David Limbrick, Jeff Leonard, Russ Geyer, Sarah Leary, Samuel Browd, Ziad Khatib, John Ragheb, Sanjiv Bhatia, Tobey MacDonald, Dolly Aguilera, Barun Brahma, Peter Manley, Susan Chi, Sabine Mueller, Anu Banerjee, Jeff Murray, Kellie Nazemi, Lissa Baird, Nathan Robison, Erin Kiehna, Mark Krieger, Eric Sandler, Philipp Aldana, Joanne Wang, Sandeep Sood, Donna Neuberg, Maneka Puligandla, Lianne Greenspan, Karen Wright, Michael Prados, Pratiti Bandopadhayay, Keith Ligon, Mark Kieran
Journal: Neuro-Oncology (2017)

INTRODUCTION: The DIPG Biology and Treatment Study (DIPG-BATS) incorporated a surgical biopsy at presentation and stratified patients to receive FDA-approved agents chosen on the basis of specific biologic targets. METHODS: Subjects were enrolled in the DIPG-BATS trial if the imaging appearance of the tumors had typical features of a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. Subjects were all treated with conventional fractionated external radiotherapy, and bevacizumab. Subjects were stratified to receive erlotinib or temozolomide, both agents, or neither agent. Whole-genome sequencing (WGS) and RNA-sequencing were performed on tumor samples but not used for treatment planning. RESULTS: Fifty-three patients were enrolled at 23 participating institutions, of which 50 underwent biopsy. The median age was 6.4 years, with a male to female ratio of 24::29. Surgical biopsies were performed using standard stereotactic techniques with a transcerebellar approach. There were no deaths attributed to the surgical procedure. Two patients experienced grade 3 toxicities during the procedure (one patient with apnea and one with hypertension). One patient experienced a neurologic deficit (left hemiparesis) that did not recover. Of the 50 patients biopsied, 46 provided sufficient tissue to perform the assays (92%, two-stage exact binomial 90% confidence interval 83–97%). CONCLUSIONS: Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that informs treatment decision making.
THERAPY OF EXOPHTHALMIC GOITER.
Journal: JAMA (1905)

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