tbuckley/cabot-search huggingface dataset:
EGFR Gene Copy Number and Response to Lapatinib/Capecitabine in HER2 Positive Metastatic Breast Cancer Patients Pretreated with Trastuzumab.
Authors: A. Fabi, V. Graziano, R. Merola, G. Metro, P. Papaldo, A. Cianciulli, M. Mottolese, I. Sperduti, E. Vico, F. Cognetti
Journal: Cancer Research (2009)

Abstract Background: Lapatinib (L) is a potent and selective dual inhibitor of EGFR and HER2. In HER2 positive metastatic breast cancer (MBC) pretreated with trastuzumab-based therapies, the association of L + Capecitabine (C) showed superior response rate (RR) and progression free survival (PFS) over C alone. We analyzed the correlation between EGFR gene copy number and clinical outcome in a population undergoing treatment with L 1250 mg daily plus C 2000 mg/m2 days 1-14 every 21. Materials and methods: EGFR gene copy number was assessed by FISH analysis in paraffin-embedded tissue blocks from 30 HER2 positive patients who had failed at least one trastuzumab-based therapy in the metastatic setting. EGFR gene status was scored as: the mean value of EGFR gene copy number (GCN) per nucleus, the mean ratio between EGFR and Chromosome 7 and the percentage of cells displaying more than 5 EGFR GCN. A receiver operating characteristic (ROC) analysis was set up to define the cut-off of mean EGFR GCN. A value greater than 3.36 was able to discriminate responders versus non-responders. The primary end point of the study was identification of the EGFR FISH score that best predicts RR Results: Twenty-five patients were evaluable for EGFR FISH analysis. No sample displayed a homogeneous amplification of the EGFR gene by ratio (EGFR gene/CEP 7 ≥2). Patients characteristics were as follows: median age 52.4 (range 32-70), visceral disease in 20 patients (80%), brain metastases in 11 patients; median number of previous trastuzumab-based therapies was 2 (1-4). Twelve patients achieved a partial response for a RR of 48% (95% CI: 28.8-64.5). At a median follow up of, PFS was 7 months (95%CI: 5-8). Median overall survival has not been reached at the time of analysis. Mean EGFR GCN was &amp;gt; 3.36 in 10/25 patients. These patients showed a significantly higher RR (n=8/10; 80%) as compared to those with mean EGFR GCN ≤3.36 (n= 4/15; 27%), (p=0.009). No significant difference in terms of PFS was seen. Conclusion: high EGFR GCN might predict for an increased likelihood of responding to L. This is the first report associating increased EGFR GCN with sensitivity to L. These results warrant further investigation on a larger sample of patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3095.
Pulmonary Granulomas in an Intravenous Drug User
Authors: R Lemoine, M Dusmet
Journal: New England Journal of Medicine (2000)

Figure 1. A 28-year-old woman with a history of heroin use was admitted for increasing dyspnea. A chest radiograph (Panel A) showed diffuse bilateral pulmonary infiltrates that were predominantly interstitial. An open-lung biopsy was performed. Histologic analysis showed medial hypertrophy of medium-sized pulmonary arteries indicative of pulmonary hypertension, as well as occasional foreign-body granulomas. Polarized light microscopy (Panel B) revealed refractile particles in the outer portion of the wall of a pulmonary artery (hematoxylin and eosin, ×40). Electron microscopy of lung tissue showed the ultrastructural aspects of the embolized microcrystalline material in an alveolar septum (arrow in Panel C, ×2100; . . .
Increase in Severity of Proximal Coronary Disease after Successful Distal Aortocoronary Grafts
Authors: GEORGE BOUSVAROS, ABDUL R. PIRACHA, MUHAMMAD A. CHAUDHRY, COLIN GRANT, THOMAS M. OLDER, ROQUE PIFARRE
Journal: Circulation (1972)

Aortocoronary vein grafts were placed in seven patients to bypass severe proximal stenosis in nine coronary arteries. Routine postoperative angiography showed patent grafts in all patients and substantial increase of proximal occlusive disease, diffusely or at the points of narrowing, in six of nine arteries (four patients), with complete obstruction of four of the six vessels. Two of the four patients experienced improvement in angina which was sustained despite the advanced proximal disease. The third patient suffered a late postoperative myocardial infarction and the fourth had recurrence of angina, both probably as a result of the increased proximal disease. The possibility is considered that a successful vein graft, by diverting flow from the poststenotic segment, may accelerate its occlusion and that consequences of advancing occlusive disease may not be prevented by vein-grafting surgery.
Basement membrane components outline the tumour islands in cylindroma
Authors: L. WEBER, G. WICK, W. GEBHART, T. KRIEG, R. TIMPL
Journal: British Journal of Dermatology (1984)

The main histological feature of cylindroma is the deposition of sheaths of a 'hyalinized' material contiguous to the tumour cell clusters. Although ultrastructural studies of this material have revealed a basement membrane-like structure, its exact nature has remained unclear. Using immuno-staining with affinity-purified antibodies directed against distinct basement membrane components, we have shown that type IV collagen and laminin are major constituents of this zone. In addition, cell culture studies indicated that both proteins are synthesized by the tumour cells. The immunohistological data make it clear that the tumour matrix between the tumour cell islands is composed not only of basement membrane components, but also is composed of other connective tissue constituents, i.e. type I and III collagen and fibronectin.
Cardiovascular and Respiratory Changes During Sleep in Normal and Hypertensive Subjects
Authors: J. D. Bristow, A. J. Honour, T. G. Pickering, P. Sleight
Journal: Cardiovascular Research (1969)

The fall of blood pressure accompanying sleep in man is largely due to a diminished peripheral resistance. Subjects with normal and raised arterial pressure show qualitatively and quantitatively similar haemodynamic changes during sleep, except that the baroreflex sensitivity in hypertensives is decreased, both awake and asleep.
Identity Problems and the Adaptation of Nurses to Severely Burned Children
Authors: SUSAN QUINBY, NORMAN R. BERNSTEIN
Journal: American Journal of Psychiatry (1971)

Caring for burned children presents a difficult challenge to the personal and professional identity of nurses. The authors studied the adjustment of new nurses in the field—their initial idealized expectations, their conflict between these goals and reality, and their resolution of this conflict. The nurses realized the unreality of their initial goals and gained a maturity that enabled them to better help the children and to enhance their own self-esteem.
Virus Specific Immune Responses after Human Neoadjuvant Adenovirus-mediated Suicide Gene Therapy for Prostate Cancer
Authors: R.R.M. van der Linden, B.L. Haagmans, P. Mongiat-Artus, G.J. van Doornum, R. Kraaij, D. Kadmon, E. Aguilar-Cordova, A.D.M.E. Osterhaus, T.H. van der Kwast, C.H. Bangma
Journal: European Urology (2005)
WHAT IS THE UNDERLYING PLAQUE MORPHOLOGY OF CORONARY THROMBOSIS? AN ANGIOSCOPIC AND VIRTUAL HISTOLOGY INTRAVASCULAR ULTRASOUND CORRELATIVE STUDY
Authors: Elias Sanidas, Akiko Maehara, Gary S. Mintz, Toshikazu Kashiyama, So-Yeon Choi, Jin Bae Lee, George Dangas, Martin Leon, Jeffrey Moses, Gregg W. Stone, Yasunori Ueda
Journal: Journal of the American College of Cardiology (2010)
Regulatory T Cell–Resistant CD8+ T Cells Induced by Glucocorticoid-Induced Tumor Necrosis Factor Receptor Signaling
Authors: Hiroyoshi Nishikawa, Takuma Kato, Michiko Hirayama, Yuki Orito, Eiichi Sato, Naozumi Harada, Sacha Gnjatic, Lloyd J. Old, Hiroshi Shiku
Journal: Cancer Research (2008)

Abstract We previously found that a Salmonella typhimurium vector engineered to secrete soluble tumor antigen induces CD4+ T cells resistant to CD4+CD25+ regulatory T cells (Treg) and that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) signal is involved in the development of this resistance. In this study, we address the potential of incorporating GITR ligand (GITRL) as a way to augment the immunogenicity of cancer vaccines. BALB/c mice were immunized by gene gun with plasmids encoding the mutated extracellular signal-regulated kinase 2 (mERK) with or without plasmids encoding mouse GITRL. Coadministration with GITRL during primary and secondary immunization enhanced the induction of mERK-specific CD8+ T cells. Antibody depletion and minigene analysis suggested that GITRL directly activated CTL epitope-specific CD8+ T cells independently of CD4+ T cells. Immunization with plasmids encoding a CTL epitope and GITRL resulted in strong tumor inhibition in a CD8+ T cell–dependent manner. Furthermore, CTL epitope-specific CD8+ T cells induced by immunization with plasmids encoding CTL epitope coadministered with GITRL were refractory to suppression by CD4+CD25+ Tregs compared with CD8+ T cells induced without GITR signaling. We propose that coadministration of GITR signaling agents with tumor antigens constitutes a promising novel strategy for cancer vaccine development. [Cancer Res 2008;68(14):5948–54]
ANEMIA IN KOREA
Authors: Zacharias Bercovitz
Journal: JAMA (1933)

To the Editor:  —In his article on anemias (The Journal, April 29, p. 1303), Ottenberg calls attention to the observation that has been made regarding the relationship of copper to the anemias. He also calls attention to the very minute quantities of copper required.  During a period of nine years' practice in Korea, the last three of which have been entirely in internal medicine in a hospital with an attendance of 50,000 patients yearly in the outpatient department, it has not been possible to make the diagnosis of pernicious anemia or sprue in a single instance. I do not wish to create the impression that pernicious anemia does not occur in Korea, but of more than 3,000 patients examined personally and in whom complete blood studies were made it has not been possible to confirm a diagnosis of pernicious anemia.  There are two other facts of at least passing interest
Abstract CT207: Pharmacokinetic analysis of the HDAC inhibitor belinostat (PXD-101) and metabolites in patients with hepatic dysfunction
Authors: Brian Kiesel, Robert Parise, Yan Lin, Deborah Allen, Guru Reddy, Shanta Chawla, Richard Piekarz, Percy Ivy, Shivaani Kumar, Jan H. Beumer
Journal: Cancer Research (2014)

Abstract Introduction: Histone deacetylases (HDAC) are frequently deregulated in human cancers and their inhibition allows re-expression of silenced genes. Belinostat is an HDAC inhibitor with in vitro and in vivo activity in multiple malignancies, currently in phase II trials. We report the pharmacokinetics of belinostat and metabolites in patients enrolled in a phase I liver dysfunction trial currently being conducted and led by the NCI. Methods: Patients enrolled into the study were assigned to varying cohorts depending on their level of hepatic dysfunction (normal=N, mild=H1, moderate=H2, and severe=H3). All patients were given a 30 minute infusion at 400 mg/m2 on cycle 1 day -7. Heparinized plasma samples were collected prior to infusion, 15 and 25 min after start, and 5, 10, 15, 30, 60, 90, 120, 240, 360, 480 and 1440 minutes after infusion. Patients from the NCIDTC had samples collected and these were quantitated by a previously validated assay for belinostat, belinostat-glucuronide, methyl-belinostat, M21, M24, and M26. Pharmacokinetic parameters were derived non-compartmentally with PK Solutions. Metabolic ratios were calculated as a measure of metabolic fate. Results: 15 patients (N=2, H1=10, H2=2, H3=1) had useable pharmacokinetic data. Observed belinostat Cmax (N=21.1±4.9, H1=55.8±78.0, H2=23.0±7.2, H3=23.1 µg/mL) and belinostat AUC0-inf (N=806±294, H1=1308±996, H2=702±82, H3=780 µg/mL•min) did not reveal any trends with dysfunction cohort. Metabolic AUC0-inf ratios of belinostat to the various metabolites also did not appear to change with dysfunction cohort. Conclusion: Liver function does not appear to affect the pharmacokinetics or metabolic fate of belinostat. Analysis of additional subjects is ongoing. The results of this study will facilitate optimal dosing for patients with liver dysfunction. Citation Format: Brian Kiesel, Robert Parise, Yan Lin, Deborah Allen, Guru Reddy, Shanta Chawla, Richard Piekarz, Percy Ivy, Shivaani Kumar, Jan H. Beumer. Pharmacokinetic analysis of the HDAC inhibitor belinostat (PXD-101) and metabolites in patients with hepatic dysfunction. [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 CT207. doi:10.1158/1538-7445.AM2014-CT207
Guiding Principles for Center for Medicare &amp; Medicaid Innovation Model Evaluations
Authors: Benjamin L. Howell, Patrick H. Conway, Rahul Rajkumar
Journal: JAMA (2015)

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
S41. Novel CEA-targeted IL2 variant immunocytokine for immunotherapy of cancer
Authors: C Klein
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Here we describe a novel class of monomeric tumor-targeted immunocytokines that comprise a single IL-2 variant (IL2v) with abolished CD25 binding that is fused to the C-terminus of a tumor specific antibody with a heterodimeric Fc devoid of FcγR and C1q binding. For tumor
Elevated Plasma Proglucagon-like Component with a Glucagon-Secreting Tumor
Authors: David N. Danforth, Timothy Triche, John L. Doppman, Robert M. Beazley, Pasqual V. Perrino, Lillian Recant
Journal: New England Journal of Medicine (1976)

To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter. Biogel column separation of the plasma immunoreactive glucagon revealed four components; the predominant component had a molecular weight of 9000 daltons and was designated as proglucagon-like. This fraction constituted 60 to 90 per cent of the total circulating immunoreactive glucagon, and had a biologic activity of 32 percent of that of an immunoequivalent amount of normal (porcine) pancreatic glucagon. After treatment with streptozocin (1.5 g per square meter) the plasma immunoreactive glucagon level decreased to 0.24 ng per milliliter. Treatment was accompanied by a marked reduction in the proglucagon-like component and the appearance of pancreatic glucagon (molecular weight of 3500 daltons) as the major post-therapy fraction. These findings support the use of streptozotocin in the management of unresectable glucagon-secreting tumors.
A World to Care For: The Autobiography of Howard A. Rusk
Authors: E. DORINDA LOEFFEL
Journal: JAMA (1973)

All physicians should read this inspiring book. The autobiography of the "father" of rehabilitation medicine, it describes the conception and development of a new medical specialty, amidst the apathy and pessimism of a skeptical medical profession. In 1942 no organized program of rehabilitative health care existed for severely injured men returning from World War II. With "broken bodies" and "broken spirits" caused by amputations, disfigurement, and spinal cord injuries, many men faced lives of custodial care filled with boredom and despair, waiting in Veterans Administration Hospitals to die of infection or disease. Slowly, Dr. Rusk, undeterred by rigid military protocol, unimaginative skeptics, and government red-tape, began to organize rehabilitation programs for these hitherto "hopeless" cases. By continuously promoting his ideas to people with the power and money to support them, he proved that one man with foresight and determination can accomplish remarkable changes in the philosophy and delivery of health
Simulated driving performance in patients with obstructive sleep apnea.
Authors: C F George, A C Boudreau, A Smiley
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To assist in determining ability to drive in patients with obstructive sleep apnea (OSA), we developed a divided attention driving test (DADT) based on the work of Moskowitz and Burns (6). We first examined its ability to detect impaired performance by testing normal subjects both sober and impaired by alcohol (mean blood alcohol level, 95 +/- 25 mg/dl). Subsequently, 21 male patients with OSA (age 49.3 +/- 12.7 [SD] yr; apnea hypopnea index [AHI] 73 +/- 29) and 21 age- and sex-matched control subjects underwent polysomnography followed by daytime sleep latency testing (MSLT). Before each day-time nap, subjects were given the DADT for 20 min. Patients who performed much worse than control subjects in all measures, with the largest difference noted in tracking error (OSA, 228 +/- 145 cm versus control 71 +/- 31 cm, p < 1 x 10(-9)). Half of the patients were worse than any control subject, with some showing performance worse than control subjects impaired by alcohol. However, MSLT and AHI explained less than 25% of the variance in tracking error, making individual prediction problematic. We concluded that in laboratory driving performance skills are markedly impaired in over half our group with sleep apnea. Further testing and comparing on-road performance should aid in predicting ability to drive.
A Device for Controlled Negative Pressure
Authors: John Bradford Millet
Journal: New England Journal of Medicine (1948)

THIS article presents a simple compact device for the safe administration of controlled negative pressure to the gastrointestinal tract of patients in institutions having built-in negative-pressure systems.Some of the difficulties and inconveniences previously encountered in the use of suction apparatus prompted the development of this device. Any apparatus, when on the floor, is likely to be tipped over or broken and makes cleaning of the room difficult. Bulky glass apparatus, if strapped on the bed frame, is likewise often broken. Many rubber tubes leading to and from the apparatus are often draped over the bed and the patient. Glass . . .
783 DIFFERENTIAL LIVER MIRNAS EXPRESSION IN CHRONIC HEPATITIS C PATIENTS AT EARLY STAGES OF LIVER FIBROSIS
Authors: E. Estrabaud, I. Bièche, M. Lapalus, S. De Muynck, O. Lada, M. Martinot-Peignoux, A. Duces, D. Valla, P. Bedossa, P. Marcellin, M. Vidaud, T. Asselah
Journal: Journal of Hepatology (2011)
Diverse regulation of atrial natriuretic peptide secretion by serotonin receptor subtypes
Authors: C CAO, J HAN, S KIM, K CHO, S KIM
Journal: Cardiovascular Research (2003)

Objective: Serotonin (5-hydroxytryptamine [5-HT]) receptors are located in peripheral tissues as well as in the central nervous system. Serotonin receptors mediate positive inotropic and chronotropic effects in atria. The aim of this study was to investigate physiological role of endogenous serotonin on the regulation of atrial natriuretic peptide (ANP) secretion from the atria. Methods: An isolated perfused nonbeating rat atrial model was used. Changes in atrial volume induced by increasing intra-atrial pressure were measured. The concentration of ANP was measured by radioimmunoassay and the translocation of ECF was measured by [3H]-inulin clearance. Results: Serotonin, an endogenous 5-HT receptor agonist, caused concentration-dependent suppressions of stretch-induced ANP secretion, which were less pronounced than those caused by α-methyl-5-HT maleate, a 5-HT2 receptor selective agonist. The suppression of stretch-induced ANP secretion due to serotonin and α-methyl-5-HT maleate was attenuated by ketanserin, a 5-HT2 receptor antagonist, and accentuated by RS23597-190, a 5-HT4 receptor antagonist. The suppressive effect of serotonin on ANP secretion was attenuated by neomycin, staurosporine, and chelerythrine. In contrast, 2-[1-(4-piperonyl)piperazinyl]benzothiazole, a 5-HT4 receptor selective agonist, caused an accentuation of stretch-induced ANP secretion, which was completely blocked by RS23597-190 and SB203186 HCl but not by ketanserin. This effect was not affected by MDL12330, KT-5720, or H-89. The intracellular Ca2+ concentration in single atrial myocytes was not changed by serotonin and agonist for either 5-HT2 or 5-HT4 receptor. Conclusions: These results suggest that atrial 5-HT2 and 5-HT4 receptor agonists have opposite actions on the regulation of ANP secretion and the suppressive effect of serotonin on the ANP secretion may act through 5-HT2 receptor and phospholipase C pathway.
Proteasome inhibitor bortezomib impairs both myelofibrosis and osteosclerosis induced by high thrombopoietin levels in mice
Authors: Orianne Wagner-Ballon, Didier F. Pisani, Thomas Gastinne, Micheline Tulliez, Ronan Chaligné, Catherine Lacout, Frédéric Auradé, Jean-Luc Villeval, Patrick Gonin, William Vainchenker, Stéphane Giraudier
Journal: Blood (2007)
Evaluating the Costs and Benefits of Outpatient Diabetes Education and Nutrition Counseling
Authors: Robert M Kaplan, Wayne K Davis
Journal: Diabetes Care (1986)

The Board of Directors of the American Diabetes Association (ADA) recently endorsed a resolution recommending third-party payment for outpatient education and nutritional counseling. One of the major rationales for the statement was that education and nutritional counseling will lead to reductions in health care costs. This article critically reviews the 13 studies cited in support of the ADA Policy Statement. Among these studies, only 2 compared a treated group with a control group. Both of the studies with control groups failed to randomly assign patients to treatment condition. Only 4 of the studies showed an accounting of program costs. Upon close inspection, it appears that some of the programs actually increased, rather than decreased, health care expenditures. Attrition from programs was reported in only a minority of cases, and was large when reported. The effect of the programs upon diabetes control was inconsistent across studies. It is suggested that the rationale for education and nutritional services be based on improved health status. In addition, the execution of a systematic experimental study to evaluate these services is urged.