tbuckley/cabot-search huggingface dataset:
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
Stories of Sickness
Authors: R. Kolarik
Journal: JAMA (2003)

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
How the NHS can improve safety and learning
Authors: P. Barach
Journal: BMJ (2000)

News p 1689 Reviews p 1738 

An Organisation with a Memory , the newly released report from England's chief medical officer on learning from adverse events in the NHS,1 joins recent high profile policy statements from the United States 2 3 and Australia 4 that acknowledge an epidemic of underreported preventable injuries due to medical management. This report should not, however, be seen as a one off response to preventable patient catastrophes—although recent celebrated cases in Britain, such as the Bristol paediatric cardiac surgery story, have provided a driving force for change. Instead, An Organisation with a Memory should be understood in the larger context of a 10 year modernisation strategy to continuously and measurably improve the quality of health care. If it is understood in this way, and the government is willing to invest in the necessary systems, training, and research, then it will prove a real force for change.

Most care in the NHS is of high clinical standard, but the chief medical officer's report suggests that as many as 850 000 serious adverse health care events might occur in the NHS hospital sector each year at a cost of over £2bn. Half of these …
Characterization of the Platelet Prostaglandin D2 Receptor
Authors: Barry Cooper, David Ahern
Journal: Journal of Clinical Investigation (1979)

Prostaglandin (PG) D(2) is synthesized in platelets at concentrations which could inhibit aggregation via activation of adenylate cyclase. To more directly define platelet-PG interactions, a binding assay has been developed for platelet PG receptors with [(3)H]PGD(2) as ligand. [(3)H]PGD(2) binding to intact platelets was saturable and rapid with the ligand bound by 3 min at 20 degrees C. PG competed with the [(3)H]PGD(2) binding site with a potency series: PGD(2) (IC(50) = 0.08 muM) >> PGI(2) (IC(50) = 2 muM) > PGE(1) (IC(50) = 6 muM) > PGF(2alpha) (IC(50) = 8 muM). Scatchard analysis of binding data from six normal subjects showed a single class of binding sites with a dissociation constant (K(d)) of 53 nM and 210 binding sites per platelet. This PGD(2) receptor assay was then used to study platelets from five patients with myeloproliferative disorders (polycythemia vera, essential thrombocythemia, and chronic myelogenous leukemia), as over 90% of these patients have platelets resistant to the effects of PGD(2) on aggregation and adenylate cyclase activity (1978. Blood.52: 618-626.). In the presence of 50 nM [(3)H]PGD(2), the patients' platelets bound 7.1+/-2.9 fmol ligand/10(8) platelets compared with 15.1+/-1 fmol/10(8) platelets in normals, a decrease of 53% (P < 0.01). Scatchard analysis showed that the K(d) of [(3)H]PGD(2) binding (33 nM) was comparable to normal platelets, which indicates that the decreased PGD(2) binding in these platelets represented fewer receptors rather than altered affinity of the ligand for the binding site. The 53% decrease in [(3)H]PGD(2) binding correlated with a 48% decrease in PGD(2)-activated platelet adenylate cyclase. The characterization of the platelet PGD(2) binding site provides further direct evidence that there are at least two PG receptors on platelets, one for PGE(1) and PGI(2), and a separate receptor for PGD(2). Direct binding analysis will be a useful tool for studying the role of PG in regulating platelet function, as demonstrated by the selective loss of PGD(2) binding sites in patients with myeloproliferative disorders.
Abstract 15232: Role of Bmp Signals in Marfan Syndrome
Authors: Yan Bai, Yuka Morikawa, Jun Wang, Ge Tao, Min Zhang, James F Martin
Journal: Circulation (2013)

Fibrillin-1 (Fbn-1) is known for Marfan syndrome (MFS), with which patients have complex symptoms found in the heart, blood vessels, bones and eyes. About 1 in 5,000 people have Marfan syndrome. Ao...
症状性胃-食管反流病:奥美拉唑或雷尼替丁间歇性治疗的双盲对照研究
Authors: 方卫纲
Journal: BMJ (1999)

目的：对症状性胃-食管反流病患者的12个月间歇性治疗效果做出评价。设计：随机的多中心的双盲对照研究。有胃灼热症状且胃镜结果正常或轻度糜烂的患者服用奥美拉唑（omeprazole）每日10mg，或20mg或者雷尼替丁（ranitidine)150mg每日2次，共2周。症状未缓解者，如服用奥美拉唑每日10mg或雷尼替了则剂量加倍再服用2周，如服用奥美拉唑每日20mg则继续服用2周。对有症状或轻度症状的患者随诊12个月。对随诊期间有中度或重度胃灼热症状复发的患者，以最初可控制症状的剂量进行治疗。时间与单位：1994～1996年，医院或初级医疗单位。研究对象：667例胃-食管反流病患者。主要结果的测量指标：休疗总时间、间歇性治疗失败的时间，以及从最好到最差的疗效分级。结果：704例患者被纳入随机分组，667例适于分析；318例接受间歇性治疗的患者未求助于胃酸抑制剂的维持治疗而到达研究的终点。对整个研究而言，在随诊期间休疗时间的中位数是142天（到达治疗相关终点的526例患者的休疗时间中位数是281天）。因此，大约有半数患者最少有6个月不需要治疗，并且这一情况在所有3个治疗组中都是相似的。在疗效分级中，378例患者（72％）为最好（无复发或者有1次或多次复发但之后完全缓解直至12个月研究结束）；630例患者（9
Abstract 12786: Wireless Transmission of a Prehospital Electrocardiogram Can be Cost Effective for Patients with ST-Elevation Myocardial Infarction
Authors: Daniel M Frendl, Joshua T Chang, Galen S Wagner, Eric L Eisenstein
Journal: Circulation (2010)

Introduction: The time benefits associated with integrated prehospital diagnostics and in-hospital care for patients with ST-elevation myocardial infarction (STEMI) are well established. However, t...
A Quick Responsive Fluorogenic pH Probe for Ovarian Tumor Imaging
Authors: Ching-Hsuan Tung, Jianjun Qi, Lingchuan Hu, Myung Shin Han, Young Kim
Journal: Theranostics (2015)

A novel cell-permeable compound, CypH-1, that is non-fluorescent at neutral pH, but fluoresces under mildly acidic conditions with a near infrared maximum emission wavelength was designed for the detection of tumors in the clinical setting.The potential of CypH-1 in ovarian cancer imaging was demonstrated using a murine model.The intraperitoneally administered CypH-1 results in a robust fluorescence signal of discrete neoplastic lesions with millimeter range resolution within few hours.Moreover, fluorescence signal is strikingly enhanced at peripheral regions of tumors at the microscopic level suggesting a sharp physiological difference at the tumor/normal tissue interface.This robust acid-activated imaging agent is expected to have significant impact in broad surgical and diagnostic applications.
Experimental myocardial infarction
Authors: Raj Kumar, William B. Hood, Julio Joison, David P. Gilmour, John C. Norman, Walter H. Abelmann
Journal: Journal of Clinical Investigation (1970)

Use of digitalis in myocardial infarction is controversial. To determine the efficacy and toxic threshold, serial infusions of 3 mug/kg per min of acetyl-strophanthidin were given to six intact conscious dogs 24 hr before and 1 hr, 2 days, and 7 days after myocardial infarction induced by inflation of a balloon cuff implanted on the left anterior descending coronary artery. Within 1 hr after myocardial infarction, heart rate increased by 28%. Left ventricular end-diastolic pressure increased from 7 to 20 mm Hg, and stroke volume decreased by 25%. At this time acetylstrophanthidin caused no beneficial hemodynamic change, 1 wk later, the heart rate and left ventricular end-diastolic pressure had declined toward normal but remained elevated. At this time, acetylstrophanthidin lowered left ventricular end-diastolic pressure by 25%, and increased the stroke volume and cardiac output by 25% and 21% respectively, without any change in heart rate or aortic pressure. Tolerance to acetylstrophanthidin, defined as appearance of ventricular tachycardia, declined the 1st hr after myocardial infarction by 24% (P<0.05) from the control level of 43 +/-4 mug/kg (SEM), but subsequently returned to control.Thus, immediately after myocardial infarction, tolerance to acetylstrophanthidin was reduced, and left ventricular failure was not ameliorated. 1 wk later in the healing phase of myocardial infarction, tolerance to acetylstrophanthidin returned to normal and left ventricular performance was improved by this drug. The study suggests a limited therapeutic role for digitalis in the treatment of left ventricular failure in the acute phase immediately after myocardial infarction, but beneficial effects may occur in the healing phase 1 wk later.
Abstract 3100: Safety and Efficacy of Transcatheter Epicardial Cryoablation - Comparison of the Lesion Size between Extra-Large Tip and Large Tip Catheter
Authors: Kenichi Hashimoto, Ichiro Watanabe, Yasuo Okumura, Kimie Ohkubo, Kazunori Kawauchi, Sonoko Ashino, Masayoshi Kofune, Atsushi Shindo, Hidezou Sugimura, Toshiko Nakai, Satoshi Saito
Journal: Circulation (2006)
Plakoglobin is differentially expressed in ARMS and ERMS rhabdomyosarcoma cells
Authors: Tamara Gastaldi, Paolo Bonvini, Agnese Marrone, Francesca Sartori, Giovanni Esposito, Achille Iolascon, Angelo Rosolen
Journal: Cancer Research (2005)

4709   Plakoglobin (γ-catenin) and β-catenin are pivotal components of cell-cell adherent junctions, linking cadherin receptors to the actin cytoskeleton. Unlike β-catenin overexpression, which is implicated in proliferation and tumor formation, high levels of plakoglobin suppress cell growth and tumorigenicity, whereas reduction of plakoglobin expression was found in highly invasive and metastatic tumors. We studied the expression of β-catenin and plakoglobin in 5 alveolar (ARMS) and 4 embryonal (ERMS) rhabdomyosarcoma (RMS) cell lines and 11 RMS tumor biopsies, 4 ARMS carrying the translocation t(2;13)(q35;q14), 2 ARMS without translocation and 3 ERMS. We found a consistent and homogeneous β-catenin expression in all of the cell lines and tumors tested, while plakoglobin, detectable in ERMS, was absent or almost undetectable in ARMS. These findings were confirmed by semi-quantitative RT-PCR assay at the RNA level. Immunocytochemical analysis of RMS cell lines showed membrane and cytoplasmic localization of β-catenin in all of them, whereas staining of plakoglobin was restricted to the cytoplasm of the ERMS cells. We did not detect any nuclear staining of both β-catenin and plakoglobin in fixed cells due, perhaps, to sensitivity limitations of the technique. However, cell fractionation analyses demonstrated that both catenins localized in the cytoplasm and in the nucleus, where they may exert transcriptional activity. Because gene silencing can be mediated by aberrant methylation and/or deacetylation of promoter regions, we assessed the effects of the DNA demethylating agent 5-Aza-2’-deoxycytidine (5AzadC) and of the histone deacetylase inhibitor Trichostatin-A (TSA). Our results suggest that plakoglobin expression is inhibited by both hypermethylation and deacetylation mechanisms in ARMS. We showed a partial restoration of plakoglobin expression in 5AzadC treated RH30 cells in a dose-dependent manner, whereas time course analysis of plakoglobin expression in TSA-treated RH30 cells showed a partial restoration in a time-dependent fashion. β-catenin expression was not increased by 5AzadC or by TSA treatments. We showed a synergistic increase in plakoglobin expression in the ARMS cells RH4 and RH30 treated with both agents. To further investigate this aspect, methylation-specific PCR of bisulfite-modified DNA was applied to assess the methylation status of promoter-associated CpG islands. RH4 and RH30 ARMS cells displayed methylated or emi-methylated alleles, respectively, whereas RD ERMS cells, which were 5AzadC unresponsive and endogenously expressed plakoglobin, contained only unmethylated alleles. These results may explain some of the biological and clinical differences between ARMS and ERMS and set the basis for a wider functional characterization of catenins in RMS and other solid tumors of childhood.
Weber's test demystified
Authors: C. E Mbubaegbu
Journal: BMJ (2002)

Suturing v conservative management of hand lacerationsAll lacerations need to be examined thoroughly Editor-Quinn et al show that conservative treatment is faster and less painful for small uncomplicated lacerations of the hand. 1 However, we think that lacerations to the hand, no matter how small, must be examined thoroughly to exclude injuries to tendons, nerves, or joints.The authors make no comment on the mechanism of injury, which is extremely important.A knife stab laceration or glass injury to the hand would make exploration of the wound mandatory.An unimpressive skin wound may hide a remarkable amount of damage to deep structures. 2 Similarly, injuries caused by thin slivers of glass produce unimpressive skin wounds but commonly divide flexor tendons and nerves in the forearm. 3 In emergency settings we think that it is crucial to take a good history from the patient about the mechanism of injury and to examine the patient thoroughly before deciding on further management of hand lacerations, albeit suturing or conservative management.In our plastic surgery unit the nurse practitioners who refer cases of hand trauma to us have all been on a hand trauma study day organised by our department.If the mechanism of injury raises any suspicion of a tendon or nerve injury, patients are referred to us and their wounds formally explored in an operating theatre.
Combined IVUS and NIRS Detection of Fibroatheromas
Authors: Soo-Jin Kang, Gary S. Mintz, Jun Pu, Stephen T. Sum, Sean P. Madden, Allen P. Burke, Ke Xu, James A. Goldstein, Gregg W. Stone, James E. Muller, Renu Virmani, Akiko Maehara
Journal: JACC. Cardiovascular imaging (2015)
Abstract 3956: Rheumatic Heart Disease Screening by Echocardiography: The Inadequacy of WHO Criteria for Optimising the Diagnosis of Subclinical Disease
Authors: Eloi Marijon, David S Celermajer, Muriel Taflet, Ana-Olga Mocumbi, Beatriz Ferreira, Daniel Sidi, Xavier Jouven
Journal: Circulation (2009)
Abstract 2200: Randomized Comparison of Dual Source Computed Tomography and 64-Slice Multi-Detector Computed Tomography for the Detection of Coronary Artery Stenoses
Authors: Ulrike Ropers, Sultan Karakaya, Martin Wechsel, Katharina Anders, Dieter Ropers, Axel Kuettner, Werner G Daniel, Willi Kalender, Werner Bautz, Stephan Achenbach
Journal: Circulation (2006)
Radiation exposure and thyroid cancer
Authors: F. S. Greenspan
Journal: JAMA (1977)

There are abundant experimental and clinical data to associate radiation exposure and thyroid cancer. The incidence of thyroid cancer increases with increasing doses of thyroidal radiation from 6.5 rads to 1,500 rads, but higher doses tend to destroy the gland and are associated with hypothyroidism rather than cancer. The peak occurrence of thyroid tumors is between five and 30 years after exposure, but a person may develop thyroid tumors as long as 50 years after irradiation. Multiple thyroidal lesions or disorders, including adenomas, thyroiditis, and hypothyroidism as well as malignant neoplasms, can occur after radiation exposure. It is imperative, therefore, to study carefully all patients with a history of radiation exposure to the gland and to observe them carefully for life. Suggestions are made for the management of thyroid disease in these patients. (<i>JAMA</i>237:2089-2091, 1977)
Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines
Authors: L L Altshuler, L Cohen, M P Szuba, V K Burt, M Gitlin, J Mintz
Journal: American Journal of Psychiatry (1996)

Given concerns about use of psychotropic medication during pregnancy, the authors reviewed the literature regarding the effects of prenatal exposure to psychotropic medications on fetal outcome.A MEDLINE search of all articles written in English from 1966 to 1995 was performed to review information on the effects of psychotropic drug use during pregnancy on fetal outcome. Where sufficient data were available and when methodologically appropriate, meta-analyses were performed to assess risk of fetal exposure by psychotropic medication class.Three primary effects are associated with medication use during pregnancy: 1) teratogenicity, 2) perinatal syndromes (neonatal toxicity), and 3) postnatal behavioral sequelae. For many drug classes there are substantial data regarding risk for teratogenicity. Tricyclic antidepressants do not seem to confer increased risk for organ dysgenesis. The available data indicate that first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies. However, the absolute risk of congenital malformations following prenatal exposure to most psychotropics is low.Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low. Use of psychotropic medications during pregnancy is appropriate in many clinical situations and should include thoughtful weighing of risk of prenatal exposure versus risk of relapse following drug discontinuation. The authors present disorder-based guidelines for psychotropic drug use during pregnancy and for psychiatrically ill women who wish to conceive.
Canada's health system should focus on primary care
Authors: David Spurgeon
Journal: BMJ (2002)

Sweeping and expensive changes have been proposed to ensure the long term sustainability of Canada's healthcare system. The proposals are contained in a report from the Royal Commission on the Future of Health Care in Canada, which was chaired by lawyer and former politician Roy Romanow.

The report's 47 detailed recommendations, which include implementation timeframes, will cost the federal government $C15bn (£6.2bn; $US9.6bn; €9.6bn) more than the budget currently forecast for health by 2005-6.

In presenting his report Romanow, former premier of the province of Saskatchewan, where Canada's Medicare was born 40 years ago, voiced his strong opposition to private, for profit healthcare programmes. Their failure, he said, was the reason for establishing Canada's public system in the first place, and Canadians were sceptical of them.
Elevated Systolic Blood Pressure and Low Fetal Hemoglobin Are Risk Factors for Silent Cerebral Infarcts in Children with Sickle Cell Anemia.
Authors: Sharada A. Sarnaik, James F. Casella, Bruce A Barton, Michele Afif, Gladstone Airewele, Brian W. Berman, Francoise Bernaudin, Thomas Coates, Beng Fuh, Helge Hartung, Mark E. Heiny, Thomas H. Howard, Baba Inusa, Rathi V. Iyer, Karen Kalinyak, Allison King, Melanie Kirby-Allen, Fenella J Kirkham, Janet L Kwiatkowski, Scott T. Miller, Julie A. Panepinto, Charles T. Quinn, Rupa Redding-Lallinger, Melissa M. Rhodes, Hernan Sabio, Suzanne Saccente, Charles Scher, Paul Telfer, Alexis A Thompson, Gerald M Woods, Michael R. DeBaun
Journal: Blood (2009)