tbuckley/cabot-search huggingface dataset:
PLX4032, a highly selective <sup>V600E</sup>BRAF kinase inhibitor: Clinical correlation of activity with pharmacokinetic and pharmacodynamic parameters in a phase I trial
Authors: I. Puzanov, K. L. Nathanson, P. B. Chapman, X. Xu, J. A. Sosman, G. A. McArthur, A. Ribas, K. B. Kim, J. F. Grippo, K. T. Flaherty
Journal: Journal of Clinical Oncology (2009)

9021 Background: PLX4032 is an oral, highly selective inhibitor of oncogenic V600E BRAF kinase currently in phase I trial. V600E BRAF mutation activates Raf/MEK/ERK pathway in multiple tumor types. We evaluated the relationship between PK, PD (pERK, Ki67, FDG-PET), tumor histology and clinical activity following PLX4032 administration in a phase I trial. Methods: In the phase I trial, 6 melanoma pts with V600E BRAF were treated with PLX4032 daily at several dose levels and tumor biopsies (baseline vs. day 15) were assessed histologically and by semi-quantitative IHC analysis (modified H-score) for pERK and Ki67. The first 4 pts received a crystalline formulation of PLX4032; the last 2 pts received a formulation with increased bioavailability. Plasma PK parameters were collected at frequent time points on Days 1, 8 and 15. FDG-PET was performed on Days 1 and 15 on last 2 pts. Results: In the first 4 pts, no histological changes were observed with treatment and all developed disease progression. All had decreased percentage of Ki67 positive nuclei (pre-Rx, range 20–60%, median 45%; post-Rx, range 5–25%, median 12.5%) and 3 of the 4 had decreased pERK levels (pre-Rx, range 50–100, median 60; post-Rx, range 10–40, median 11). Mean PLX4032 AUC 0–24h ∼ 126 μM*h was in the range for preclinical tumor stasis but below the threshold for shrinkage. In the last 2 pts, striking tumor necrosis and tumor melanosis was observed in the post-Rx samples. One pt remains on study with a confirmed PR, the other showed a clinical response before disease progression occurred in cycle 2. The percentage of Ki67 positive nuclei declined substantially (pre-Rx, 30% and 50% to post-Rx, 5% and 3%), as did the levels of pERK in the pt with PR (pre-Rx: 70 to post-Rx: 2). Mean PLX4032 AUC 0–24h was well above the preclinical threshold in the range of 500 - 1000 μM*h. Both pts had decreased FDG uptake on D15. Conclusions: Clinical activity of PLX4032 treatment correlates with drug exposure levels as measured by AUC 0–24h and was associated with histological changes in V600E BRAF positive melanomas on Day 15. Reduction of pERK, along with evidence of reduced proliferation and FDG uptake was observed. Further analysis of PD markers with additional pts at the MTD is planned. [Table: see text]
Sex and Social Health. A Manual for the Study of Social Hygiene.
Authors: Thomas Walton Galloway
Journal: JAMA (1924)

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
Presentation of Clinical Data
Authors: Bert Spilker, John Schoenfelder
Journal: Annals of Internal Medicine (1990)

How to Use This Book Tools of the Trade Choosing Formats and Preparing Slides Illustrating Study Designs Demographics and Patient Accountability Vital Signs Laboratory Data Adverse Reactions Efficacy Pharmacokinetics Quality of Life Compliance, Concomitant Therapy, and Cost-Effectiveness Metaanalyses Complex or Confusing Presentations
On Nicotinic Acid: Especially Methods for Its Quantitative Estimation in Organic Material
Authors: Erik Bandier, P. G. Lund
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
Abstract 1590: Autophagic Processing Of Ubiquitinated Protein Aggregates During Unloading-induced Cardiac Atrophy
Authors: Andrew G Blagg, Hongxin Zhu, Beverly A Rothermel, Joseph A Hill
Journal: Circulation (2008)

Background: Mechanical unloading of the diseased ventricle has emerged as an important treatment strategy in advanced heart failure. In rare instances, dramatic improvements in ventricular performance are seen, yet little is known regarding underlying mechanisms. Autophagy is an ancient mechanism of bulk protein degradation recently shown to be activated by a variety of forms of cardiac stress. Methods and Results: To test for a role of autophagy in atrophic remodeling of the unloaded left ventricle (LV), murine wild-type (WT) and “autophagy reporter” (αMHC-GFP-LC3 transgenic) hearts underwent heterotopic transplantation into the abdomen of same-strain recipient mice. The donor hearts were thereby mechanically unloaded while the native recipient hearts served as controls. In WT hearts, cardiomyocyte cell surface area declined 27±2% at 7 days. Processing of LC3 (microtubule-associated light chain 3) increased in atrophying donor hearts, indicative of increased autophagosome formation. Further, significant increases in the number of GFP-LC3 puncta in “autophagy reporter” hearts were observed. Levels of the pro-autophagic protein Beclin 1 increased in donor hearts, further evidence of increased autophagic flux during atrophic remodeling. In atrophic donor hearts, we detected significant increases in polyubiquitinated proteins as well as in the abundance of the ER chaperone proteins GRP78/BIP and GRP94, indicative of an unfolded protein response. As autophagy degrades numerous cellular components including polyubiquitinated protein aggregates, we transplanted hearts haploin-sufficient for beclin 1 , a gene required for early processing of autophagosomes (≈50% decrease in autophagy). In these studies, we detected robust increases in the abundance of polyubiquitin proteins in beclin 1 ± donor hearts relative to WT (62% vs 12%, p&lt;0.05). Conclusions: Autophagy is activated during cardiac atrophy and participates in processing of protein aggregates. Together, these findings implicate autophagic activity in the remodeling of the unloaded LV. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma &amp; Texas).
Category specificity in mind and brain?
Authors: Glyn W. Humphreys, Emer M. E. Forde
Journal: Behavioral and Brain Sciences (2001)

We summarise and respond to the main points made by the commentators on our target article, which concern: (1) whether structural similarity can play a causal role in normal object identification and in neuropsychological deficits for living things, (2) the nature of our structural knowledge of the world, (3) the relations between sensory and functional knowledge of objects, and the nature of our functional knowledge about living things, (4) whether we need to posit a “core” semantic system, (5) arguments that can be marshalled from evidence on functional imaging, (6) the causal mechanisms by which category differences can emerge in object representations, and (7) the nature of our knowledge about categories other than living and nonliving things. We also highlight points raised in our article that seem to be accepted.
Transesophageal endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) and PET for mediastinal staging in lung cancer
Authors: A. Chopitea, I. Fernández-Urién, A. Viúdez, M. J. García Velloso, M. D. Lozano, J. L. Pérez Gracia, A. Gúrpide, J. C. Subtil, J. García-Foncillas, J. M. López-Picazo
Journal: Journal of Clinical Oncology (2005)

7229 Background: Nodal status separates the operable patients with lung cancer (LC) from the non-operable patients. Positron emission tomography (PET) has demonstrated high sensitivity in the detection of mediastinal lymph nodes. PET false positives occurs in approximately 15%, so histophathological confirmation by invasive techniques as the mediastinoscopy is required. EUS-FNA is a minimally invasive alternative. Our objective is to determinate the safety and effectiveness of the EUS-FNA and PET in the diagnosis and staging of LC. Methods: Patients with suspected or confirmed LC underwent EUS-FNA. EUS was performed by a radial echoendoscope Olympus GF-UMQ 130 to locate lymph nodes and a linear-array echoendoscope Olympus GF-UC 30P with a 22G needle for puncture and aspiration. This technique requires sedation with propophol endovenous and an on-site cytopathologist to evaluate each sample. EUS-FNA does not need hospitalitation. Results: Thirty-seven patients with LC (32 male, mean age: 62 years) were evaluated by EUS-FNA. The indications for the EUS-FNA were material obtention for diagnosis (27 patients; 59.4%); N staging (11; 29.7%); T3 vs. T4 staging (2; 5.4%) and relapse assessment (8; 21.6%). Twenty-six of 27 patients (96.3%) in which the indication was material obtention, this was achieved. In all suspected patients to have a relapse adequate sample was obtained. Five (62.5%) were confirmed to have a relapse and in the other three (37.5%) cytology did not show malignant cells. Simultaneous EUS-FNA and PET were performed in 18 patients. Sixteen (88.9%) showed hypercaptation in mediastinum. In 12 (75%) malignancy was confirmed by EUS-FNA, and the other 4 (25%) were considered false positives (positive predictive value: 75%) Two patients (11.1%) with negative PET did not demonstrate malignant cells at EUS-FNA. Staging in two patients (5.4%) was changed from IIIA to IIIB. No patients had complications related to EUS-FNA. Conclusion: Our data suggests that EUS-FNA is a safe and effective technique for the diagnosis and mediastinal staging in patients with LC. In this way, it could allow pathological confirmation of the suspicious lesions demonstrated at PET studies. No significant financial relationships to disclose.
After the A Bomb: Emergency Care in Atomic Warfare
Authors: Charles F. Behrens
Journal: JAMA (1952)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Therapeutic effects of fractionated radioimmunotherapy (RAIT) with clivatuzumab tetraxetan combined with low-dose gemcitabine (Gem) in advanced pancreatic cancer (APC).
Authors: A. J. Ocean, M. J. Guarino, K. L. Pennington, B. H. O'Neil, C. S. Rocha Lima, T. S. Bekaii-Saab, S. A. Gulec, D. V. Gold, W. A. Wegener, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2010)

4115 Background: Since a single dose of 90Y-labeled anti-mucin humanized mAb, clivatuzumab tetraxetan (90Y-hPAM4), showed transient objective antitumor activity in APC, we are evaluating repeated treatment cycles plus low-dose Gem in a phase I/II trial. Methods: Pts with untreated, inoperable, stage 3/4 APC received 200 mg/m2 Gem once-weekly × 4 with 90Y-hPAM4 on wks 2-4, with cycles repeated until progression or unacceptable NCI-CTCv3 toxicity. The 90Y-dose was escalated by a 3+3 cohort design, with tumor responses assessed by CT, FDG/PET and serum CA19.9 after each cycle (initially every 4 wks). Results: Twenty-seven pts (10F/17M, 40-75 yrs, ECOG 0-1, 24 stage 4) received 90Y doses of 6.5 (n = 4), 9 (n = 4), 12 (n = 14) and 15 (n = 5) mCi/m2 × 3. Treatment was well-tolerated with few non-hematological side effects, including 11 pts retreated with 1-3 additional cycles. Despite higher cumulative 90Y doses, Grade 3-4 thrombocytopenia or neutropenia was manageable and reversible, even after 4 cycles, except for one pt with extensive marrow tumor infiltration. Of 22 pts now with responses assessed by CT, the disease control rate (CR + PR + SD) was 68%, including 5 pts (23%) with PR and 10 pts (45%) with SD as best response by RECIST criteria. After cycle 1, 8/17 pts (47%) improved by PET studies (negative or > 25% reduced uptake), and 6/16 (38%) with elevated baseline CA19.9 serum titers had > 50% decreases. Responses increased with higher 90Y doses, since pts treated at ≥12 mCi/m2 vs. ≤9 mCi/m2 had 4/15 vs. 1/7 PRs, 6/12 vs. 2/5 PET improvements, and 5/11 vs.1/5 CA19.9 decreases, respectively. PFS and OS data need more follow-up, particularly at higher 90Y doses, but extended survival of up to 14.8 months post therapy onset has been observed, with 8 pts currently achieving a survival > 6 months (3 pts >1 yr). Anecdotal reports indicate performance status and pain level improved with therapy, which needs validation. Conclusions: Fractionated 90Y-hPAM4 plus low-dose Gem showed therapeutic activity at current 90Y dose levels, with manageable hematological toxicity, even after 4 cycles. Dose exploration is continuing, including higher Gem doses and adding maintenance Gem. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunomedics Immunomedics Immunomedics
Grand Rounds: One Hundred Years of Internal Medicine
Authors: Russell C. Maulitz, Diana E. Long
Journal: Annals of Internal Medicine (1989)

ReviewsGrmek is admirably receptive to the socio-cultural shaping of responses to epidemic disease.Pointing out the irony of the fact that Susan Sontag's Illness as metaphor (1979) appeared on the very brink of the emergence of AIDS, he draws upon her perception that every age gets the symbolic disease it deserves to explore the metaphorical freighting of AIDS.Clearly aware that the ban upon figurative language called for by Miss Sontag in her AIDS and its metaphors (1988) flies in the face of all history, Grmek shows how the traditional metaphors surrounding epidemics have been conscripted both to fight the spread of the infection as well as to stigmatize sufferers.Not least, the historian cannot be hors de combat.Unashamedly using the language of "la lutte contre cette maladie", Grmek shows in a superb concluding chapter (aptly titled 'Grandeurs et Miseres de la Medecine Moderne') that the AIDS epidemic is the creation of a modern world, another of whose creations-scientific medicine-offers us our only hope of
The Psychology of Functional Neuroses.
Authors: Harry Levi Hollingworth
Journal: JAMA (1921)

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
Abstract 75: Time to Awakening Is Often Delayed After Therapeutic Hypothermia for Post--Cardiac Arrest Patients
Authors: Robert Swor, Ashley Pinawin, Kelly Sawyer, Dawn Jung, Nancy J Devore, Diane Capoccia
Journal: Circulation (2012)

Introduction Withdrawal of care in patients after cardiac arrest has traditionally been based on the neurological exam at 72 hours after hospital arrival. For patients receiving post-cardiac arrest therapeutic hypothermia (TH), however, there is limited data to guide prognostication. We sought to describe the time to awakening for patients treated with TH and the relationships between time to awakening and outcome. Methods We performed a retrospective chart review of adult (age &gt; 18) cardiac arrest patients from January 2006 to January 2012 who were subsequently treated with TH at a large, academic community hospital. We abstracted demographic data, neurological assessments recorded by ICU nurses, including Glasgow Coma Scale (GCS), and survival data, including cerebral performance category (CPC) at discharge. We abstracted time intervals including intervals from arrival to target temperature (33.5°), interval to rewarming (35°C), and interval from arrival and rewarming to awakening. We defined awakening as GCS greater than 8, or GCS motor &gt;4 for intubated patients. Our primary outcome measure was good neurological outcome at discharge (CPC of 1 or 2). Descriptive statistics are reported. Results During the study period, 96 patients received TH (average age 60.3 years, 64.2% male). Overall, 39 (40.6%) patients survived to discharge, six were excluded (five did not awaken, one missing time data). Time (median, IQR) from ED arrival to rewarming was 41.0 (39,43) hours, ED arrival to awakening was 52.8 (43, 89) hours, and awakening to rewarming was 12.0 (2, 42) hours. The relationship between awakening and outcome is shown in table 1. Conclusion Although most patients with a good outcome awoke within 72 hours of hospital arrival or shortly after rewarming, a number of patients had awakening delayed more than 72 hours post arrival and rewarming. Our results support the need for longer periods of observation to determine outcomes for patients who receive post arrest TH.
Abstract 15915: A Polymorphism in Activating Fcgr2a Associates With Kawasaki Disease (KD) Susceptibility, IVIG Response, and Coronary Artery Inflammation
Authors: Sadeep Shrestha, Howard W Wiener, Aditi Shendre, Jeffrey C Edberg, Michael A Portman
Journal: Circulation (2011)

Host genetic factors play a role in KD susceptibility and treatment response. Our prior studies showed that a polymorphism in the promoter of the inhibitory FcγRIIB influenced IVIG treatment respon...
Is ST segment elevation non–Q- wave myocardial infarction after thrombolytic therapy a new clinical entity that requires an invasive management strategy?∗∗Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Bernard R Chaitman, Saad R Bitar
Journal: Journal of the American College of Cardiology (2001)
Analysis of immunohistochemical predictors of outcome in pseudomyxoma peritonei
Authors: J. M. Foster, T. E. Grotz, K. K. Turaga, Z. Gatalica, P. Sharma, B. W. Loggie
Journal: Journal of Clinical Oncology (2008)

22067 Background: PMP is a rare malignant process presenting with a broad range of biological behavior, varying from the indolent course of disseminated peritoneal adenomucinosis (DPAM) to the aggressive peritoneal mucinous carcinomatosis (PMCA). However, there is overlap in the tumor biology not captured by this histological classification, and better prognostic tools need to be identified. In this study we investigated the value of immunohistochemical markers (IHC) in predicting histological subtypes and mortality in PMP patients. Methods: We retrospectively reviewed the charts of 65 patients treated between October 1, 2002 and September 31, 2006. All patients were treated with aggressive cytoreduction and IPHC with mitomycin C. Tumors were categorized into DPAM, PMCA and PMCA-I, an intermediate subtype. IHC expression of Cox-II, Her-2, EGFR, MUC-2, and Ki-67 as well as ploidy status were determined. Using Chi-Square test we determined the predictive value of these markers for PMP histological classification, while impact on survival was investigated using Kaplan-Meier survival analysis (KM). Results: Of the 65 PMP patients, the histological classification was 41% DPAM, 34% PMCA-I and 25% PMCA. With a median follow up of 16 months, patients with DPAM had a lower mortality rate of 4% compared to 17.4% PMCA-I and 25% PMCA (Table 1). The expression of EGFR, aneuploidy, and a Ki-67 score > 50% correlated progressively with the more aggressive histological subtypes (Table1). Fifteen percent of patients (n=10) died due to progressive disease. Mortality was associated with Ki-67 (p=0.03) and aneuploidy (p=0.05), but not with histological classifications evident on survival analysis. Conclusion: Expression of EGFR, high Ki-67 score, and aneuploidy appear to predict for the more aggressive histological variants (PMCA/PMCA-I). Additionally, high Ki-67 score and aneuploidy were associated with mortality independent of PMP subtype, and may represent a more sensitive tool for predicting outcome. Table 1 DPAM (N = 27) PMCA-I (N = 22) PMCA (N = 16) p-value Median Age 46 46 46 0.97 Mortality 2 (7%) 4 (18.2%) 4 (25%) 0.27 COX-II 10 (37%) 8 (36.4%) 7 (43.7%) 0.94 EGFR 10 (37%) 17 (77%) 13 (81.2%) 0.004 HER2 16 (59%) 12 (54%) 10 (66%) 0.56 Ki-67 > 50% 1 (4%) 5 (22%) 6 (37%) 0.01 Aneuploidy 1 (4%) 7 (32%) 6 (37%) 0.01 No significant financial relationships to disclose.