tbuckley/cabot-search huggingface dataset:
Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer.
Authors: Edward Samuel James, Gina Chung, Noelle Marie Sowers, Mary Beth Clark, Rebecca Lilian, Gineesha Abraham, Susan Chmael, Michelle Cappiello, Michael DiGiovanna, Erin Wysong Hofstatter, Tara Beth Sanft, Gary M. Israel, Lajos Pusztai, Lyndsay Harris, Maysa M. Abu-Khalaf
Journal: Journal of Clinical Oncology (2013)

154 Background: Synergy between histone deacetylase inhibitors and 5-fluorouracil is thought to be due to down regulation of thymidylate synthase. Study objectives are to assess maximum tolerated dose (MTD), dose limiting toxicities (DLT) and objective response rate of vorinostat (V) in combination with capecitabine (C). Secondary aims are pharmacodynamics of V. Methods: Cohorts of 3-6 patients (pts) were enrolled on a 3+3 dose-escalation phase to assess MTD of escalating doses of oral C (1500/1800/2000mg) with V 200 mg BID on days 1-7 and 15-21 of a 28 d cycle. 10 pts enrolled on dose expansion phase and treated at MTD. Pts received a “run in” treatment of V for 5 d and pre/post V biopsy (bx) collected when feasible. DLT was defined as ≥ grade 3 non hematological toxicity, grade 4 thrombocytopenia, grade 4 neutropenia &gt; 5 d, grade 4 febrile neutropenia requiring hospitalization, QTc &gt;500ms,or treatment delay &gt; 2 weeks from toxicity. Microarray analysis was performed using Illumina HT-12 gene arrays on pre/post bx from 4 pts. Results: 23 ptswith median age 51 (range 33-69) were treated: 8 pts at 1500/200mg, 5 pts at 1800/200mg, and 10 pts treated on dose expansion phase at 1500/200mg. Median # of prior lines of chemotherapy was 2 (range 0-7). 3 pts are still on study. Median # of cycles on study were 2 (range 1-42). Cycle 1 DLT was grade 3 fatigue in 2 pts treated on 1800/200mg, and in 1 pt treated on 1500/200mg. Other grade 3/4 toxicities are summarized in the Table. 14 pts are evaluable for response (12 pts at 1500/200mg and 2 pts at 1800/200mg). No objective responses were seen, 3 pts had stable disease &gt; 6 months (1 pt completed 42 cycles). All post V bx converged on principal components analysis. Changes in pathways involved in extracellular matrix and TGFb pathway were noted. Conclusions: DLT of C concomitant with V was fatigue. MTD was 1500 mg C combined with 200 mg V BID. Combination has modest clinical activity. Gene expression profiles suggest consistent pathway modulation with V. Clinical trial information: NCT00719875. [Table: see text]
Chemicals Associated with Site-Specific Neoplasia in 1394 Long-Term Carcinogenesis Experiments in Laboratory Rodents
Authors: James Huff, Joseph Cirvello, Joseph Haseman, John Bucher
Journal: Environmental Health Perspectives (1991)

The carcinogenicity data base used for this paper originated in the late 1960s by the National Cancer Institute and since 1978 has been continued and made more comprehensive by the National Toxicology Program. The extensive files contain among other sets of information detailed pathology data on more than 400 long-term (most often 24 month) chemical carcinogenesis studies, comprised of nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity. Using the current data set of 379 studies made up of 1394 experiments, we have compiled listings of chemicals having like carcinogenic target sites for each of the 34 organs or systems for which histopathology diagnoses have been recorded routinely. The most common tumor site is the liver (15% of all experiments), followed in rank order by: lung, hematopoietic system and kidneys, mammary glands, forestomach, thyroid glands, Zymbal glands, urinary bladder, skin and uterus/cervix, and circulatory system and adrenal glands. These compilations are most useful for maintaining a historic perspective when evaluating the carcinogenicity of contemporary experiments. Equally important, the chemical-tumor-organ connection permits an evaluation of how well chemically induced cancers in a particular organ in one sex or species will predict or correlate with the other sex or species. Using liver cancers as an example, the overall interspecies concordance is 80%. Likewise target site predictions can be made for chemicals selected for study that may be similar to those already evaluated; thereby experimental protocols could be adjusted to allow, for example, more extensive pathology on preselected target organs (i.e., serial sections of the kidney). Further from these observations, one could decide to use two strains of mice to evaluate a short-chain chlorinated aliphatic compound or to study a human carcinogen in a sex-species known to develop chemically induced tumors in the same site observed in humans. Structural classes of chemicals having a propensity for certain organs can be easily identified from these data. Sex-species responders to particular induced cancers become clearly evident, such as in the ovary of female mice or in the kidney of male rats.
Hemolytic Crisis in Rh-Positive Women
Journal: JAMA (1965)

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
Suppression of Oculocardiac Reflex
Journal: JAMA (1963)

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
W.W. KEEN (1837-1932) PHILADELPHIA SURGEON
Journal: JAMA (1967)

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
Comparative Biology of Test Species
Authors: Edward J. Calabrese
Journal: Environmental Health Perspectives (1988)

This paper assesses the capacity of animal models to predict human response to carcinogenic agents with consideration for the heterogeneity of humans. It is widely accepted that human susceptibility to toxic substances, including carcinogens, is highly variable. Conventional rodent models are usually highly inbred and valued for their ability to display characteristic homogeneity. Current practice assumes that the homogeneity of response to toxic agents, including carcinogens, in the rodent model will be representative of humans. The issue then becomes, To which of the broad spectrum of human responses are specific animal models likely to be related? This paper examines the extent of human heterogeneity over a broad range of biochemical characteristics (e.g., aryl hydrocarbon hydroxylase activity, epoxide hydrase activity, beta-glucuronidase activity, debrisoquine hydroxylation, DNA-adduct formation) with emphasis on those biochemical characteristics that affect responses to carcinogens. Examples are presented to compare the heterogeneity of selected animal models for these biochemical characteristics as they relate to the spectrum of human responses noted above. The paper presents a theoretical perspective for determining to which part of the human population response spectrum common animal models are most likely to be extrapolated.
Effect of erythrocytapheresis on arterial oxygen saturation and hemoglobin oxygen affinity in patients with sickle cell disease
Authors: Kou Uchida, Wayne R. Rackoff, Kwaku Ohene‐Frempong, Haewon C. Kim, Michael P. Reilly, Toshio Asakura
Journal: American Journal of Hematology (1998)

An important purpose of blood transfusion in patients with sickle cell disease is to improve arterial oxygen saturation (SaO 2 ) and thereby reduce red cell sickling.To investigate the degree of improvement in SaO 2 by blood transfusion, we determined the hemoglobin oxygen affinity, transcutaneous oxygen saturation (Tc-SO 2 ), and pulse rate before and after automated partial exchange transfusion (erythrocytapheresis).In 13 patients with sickle cell disease who underwent 24 erythrocytapheresis procedures, the mean oxygen tension at half saturation (P50) was significantly reduced from 30.4 ± 2.2 to 26.0 ± 1.6 mm Hg (P < 0.01) immediately after exchange transfusion.Mean Tc-SO 2 values increased from 96.2 ± 2.8 to 98.5 ± 2.1% (P < 0.01).Approximately 50% of the increase in Tc-SO 2 after erythrocytapheresis could be explained by the increase in hemoglobin oxygen affinity.An increase in arterial oxygen pressure (PaO 2 ) following erythrocytapheresis, suggested by the calculated PaO 2 in this study, may explain some of the increase in Tc-SO 2 .We conclude that improvement in Tc-SO 2 in patients with sickle cell disease resulted from changes in hemoglobin oxygen affinity as well as blood oxygen pressure following erythrocytapheresis.Am.
JOSEPH BLACK— REDISCOVERER OF FIXED AIR
Journal: JAMA (1966)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Use of Anticoagulants During Pregnancy
Authors: Ronald Feldman
Journal: JAMA (1963)

<h3>To the Editor:</h3> —Dr. Irving S. Wright's comments (<i>JAMA</i><b>183</b>:186 [Jan 19] 1963) about the treatment of thrombophlebitis include the suggestion that pregnant patients with this condition are particularly prone to developing pulmonary embolism, and should be treated with anticoagulants. With this I agree wholeheartedly,<sup>1</sup>but I wonder about the discontinuation of anticoagulants before delivery. We did not encounter undue bleeding despite the maintenance of therapeutic levels of anticoagulants. I would appreciate Dr. Wright's comments concerning the rapid cessation of anticoagulants for the gravid patient and the wisdom of maintaining therapy into the postpartum period.
Nobelists take genetics from bench to bedside
Authors: B. Merz
Journal: JAMA (1985)

"I can think of no other work in modern medical research—carried out by only two persons—that has been as productive as the achievements of Brown and Goldstein," said Arno Motulsky, MD, director, Center for Inherited Diseases, University of Washington School of Medicine, Seattle. Motulsky was performing what has become a ritual at medical research meetings—the presentation of an award to Michael Brown, MD, and Joseph Goldstein, MD, professors of genetics at the University of Texas Health Sciences Center in Dallas (<i>JAMA</i>[MEDICAL NEWS] 1985;254:2872). The two were receiving the American Society of Human Genetics' highest honor, the William Allan Award, at the organization's annual meeting in Salt Lake City. Three days later they would learn that they would receive the 1985 Nobel Prize for Physiology or Medicine (in Stockholm this week, on Dec 10). These citations are being added to a spate of others, including the prestigious Lasker award for
Otolaryngology-Head and Neck Surgery
Authors: Byron J. Bailey
Journal: JAMA (1984)

Virtually every branch of the specialty of otolaryngology-head and neck surgery has benefited from significant advances. Remarkable strides have been reported in the treatment of sensorineural deafness with the use of an implanted cochlear prosthesis (a miniaturized electronic transducer designed to stimulate electrically the remaining population of eighth-nerve neurons in the cochlea of profoundly deaf persons). The patients receiving implants benefit from this procedure by their ability to discriminate sound intensity differences and pitch differences below 500 to 1,000 Hz (low-frequency sounds). They are not able to understand speech, but they can distinguish differences in the duration and rhythm of sounds, and they are better able to appreciate different environmental sounds and to communicate with others by speech reading (lip-reading). House et al<sup>1</sup>report that these encouraging improvements are seen in a study series of 43 deaf children who received cochlear implants. Although a number of technical, surgical, economic,
Journal of Trauma, Baltimore
Journal: JAMA (1966)

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
Immunologic Aspects of Cardiovascular Disease
Authors: Dennis K. Ledford
Journal: JAMA (1992)

THE PRIMARY immunologic diseases of the blood vessels are termed<i>vasculitis</i>and of the heart,<i>carditis</i>. Histological characteristics of these disorders are deposition in the affected tissue of immunoglobulin and complement and/ or an inflammatory cellular infiltration without local infection, trauma, bland thrombosis, or foreign body. Proposed mechanisms of immune injury include tissue modification or immunologic exposure by previous infection or trauma resulting in an autoimmune process; immunologic response to unrelated antigens cross-reacting with vascular or cardiac antigens; and passive deposition of blood-borne immune reactants.<sup>1</sup>The classification scheme is primarily descriptive because the etiology and principal pathophysiological mechanism of most of the immunologic cardiovascular diseases are unknown. <h3>CARDITIS</h3> Carditis is a descriptive term for inflammation of any one of the three tissues of the heart (pericarditis, myocarditis, endocarditis) or of all three (pancarditis). Symptoms and signs suggest the portion of the heart involved—chest pain and accumulation of pericardial fluid
Inhaled nitric oxide used as a bridge to heart-lung transplantation in a patient with end-stage pulmonary hypertension.
Authors: G I Snell, R F Salamonsen, P Bergin, D S Esmore, S Khan, T J Williams
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We describe a 40-yr-old woman who received inhaled nitric oxide (NO) as a therapeutic bridge to heart-lung transplantation for end-stage primary pulmonary hypertension. After 10 yr of increasing disability, the patient presented in October 1993 with severe dyspnea, right ventricular angina, and syncope. As predicted by a prior vasodilator trial, prostacyclin produced as initial favorable clinical and hemodynamic response. With the recurrence of severe symptoms and hemodynamic compromise, inhaled NO was successfully tried at 40 ppm, initially via a face mask and later via a transtracheal Scoop catheter. The patient was "bridged" to heart-lung transplant after 68 d of therapy (mean dose of NO, 50.4 +/- 23 ppm). The explanted lungs revealed no evidence of significant NO toxicity, and the explanted heart was successfully transplanted into another patient. Inhalation of NO via a transtracheal catheter is a useful and practical treatment of refractory pulmonary hypertension. The limits of NO therapy in terms of duration and dosage have not been determined.
Abstract 2175: Magnitude and Time Course of Platelet Inhibition with Extended Release Dipyridamole with or without Aspirin in Healthy Japanese Volunteers: The AGgrenox versus Aspirin Therapy Evaluation (AGATE-Japan)
Authors: Victor L Serebruany, Alex Malinin, Dan Hanley
Journal: Circulation (2007)

Background: Randomized trials showed greater stroke prevention with extended release dipyridamole in combination with low dose aspirin than either with aspirin or dipyridamole alone. However, most studies with this formulation (Aggrenox®) were done in Europe and North America. Considering potential inter-racial differences in drug response, we conducted a small randomized study in healthy Japanese volunteers to compare antiplatelet regimens with regard to the changes in the platelet biomarkers. Methods: Thirty healthy volunteers (18–40 years old, 15 male and 15 female) of Japanese descend were randomized to Aggrenox® (n=17) or aspirin 81 mg (n=13 volunteers) for 30 days. Platelet function was assessed at baseline, and days 15, and 30 by conventional aggregometry, whole blood flow cytometry, and cartridge-based analyzer. Results: Both Aggrenox® and aspirin provided sustained platelet inhibition at Day 15 and Day 30. Therapy with Aggrenox®, however, was associated with more prominent and significant inhibition of collagen-induced aggregation (p=0.08, Day 15), as well as prolongation of the closure time (p=0.001, Day 30); diminished expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) (p=0.02, Day 30), glycoprotein IIb (GPIIb) antigen (p=0.001 and 0.024 for Day 15 and Day 30), and GPIIb/IIIa activity by PAC-1 antibody (p = 0.014 and 0.03), CD62 (P-selectin) (p = 0.03 for Day 15 and Day 30), as well as inhibition of protease activated receptors (PAR-1) associated with intact WEDE-15 (p = 0.002 and 0.003) and SPAN-12 (p = 0.002 and 0.04) thrombin receptors when compared with aspirin. Conclusion: The magnitude and durability of platelet response after Aggrenox in healthy Japanese is similar to those effects observed in Caucasians and African-Americans. Larger study to assess drug efficacy and safety in the Japanese post-stroke patients is warranted.
THE ATLANTIC CITY SESSION
Journal: JAMA (1934)

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