tbuckley/cabot-search huggingface dataset:
Abstract LB-75: Blood-based molecular detection of acquired resistance to anti-EGFR therapies in colorectal cancer patients.
Authors: Giulia Siravegna, Andrea Sartore Bianchi, Andrea Cassingena, Katia Bencardino, Luis A. Diaz, Mark Sausen, Victor E. Velculescu, Federica Di Nicolantonio, Salvatore Siena, Alberto Bardelli
Journal: Cancer Research (2013)

Abstract The anti EGFR monoclonal antibodies cetuximab and panitumumab are used to treat metastatic colorectal cancer patients. The clinical efficacy of EGFR inhibitors is limited by the development of acquired resistance, which typically occurs within 3-12 months since starting of therapy. We recently reported that secondary KRAS mutations are responsible for acquired resistance in approximately 50% of patients (Misale et al.; Diaz et al., Nature 2012). We reasoned that the detection of KRAS mutant alleles in the plasma of cetuximab treated patients may enable the early identification of secondary resistance to anti EGFR blockade before radiographic documentation of relapse. Using the highly sensitive BEAMing approach we have examined cell-free circulating tumor DNA (ctDNA), a form of "liquid biopsy". KRAS mutant alleles emerged in the circulation of approximately 50% of patients treated with anti-EGFR antibodies months before radiographic documentation of disease progression. The liquid biopsy approach was then used to select patients in which KRAS mutations did not emerge during anti-EGFR therapy. Exome sequencing identified amplification of the MET proto-oncogene in biopsies from patients who did not develop KRAS mutations. Using an innovative approach, we find that MET amplification can be identified in a non-invasive manner through the examination of ctDNA months before relapse becomes clinically manifest. As multiple anti-MET therapeutic strategies are available, these findings offer immediate novel opportunities to design clinical studies. Citation Format: Giulia Siravegna, Andrea Sartore Bianchi, Andrea Cassingena, Katia Bencardino, Luis A. Diaz, Mark Sausen, Victor E. Velculescu, Federica Di Nicolantonio, Salvatore Siena, Alberto Bardelli. Blood-based molecular detection of acquired resistance to anti-EGFR therapies in colorectal cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-75. doi:10.1158/1538-7445.AM2013-LB-75
The History of Mental Retardation: Collected Papers
Authors: George Mora
Journal: JAMA (1977)

These two volumes review the advances made in the last century in the care of the mentally retarded, from the mid-19th century to the present. Each section is preceded by an introduction by the three editors. The selection opens with the "Memorial to the Legislature of Massachusetts," written by Dorothea L. Dix in 1843, and ends with a 1971 article that, significantly, bears the title "Will there always be an institution?" Led by Dix's moving memorial, the first group of papers deals with rising humanitarian feelings toward the mentally retarded. The second group of articles, outstanding among which are those by E. Seguin (the Frenchborn physician who was instrumental in establishing important programs in this country), deals with the opening of the first schools for retarded, under both public and private auspices. In the latter part of the 19th century, the belief in phrenology was being replaced by more sober
American Heart Association–Bugher Foundation Centers for Molecular Biology in the Cardiovascular System
Authors: Howard E. Morgan, Sheryl R. Paul
Journal: Circulation (1995)

The American Heart Association (AHA) and the Henrietta B. and Frederick H. Bugher Foundation in 1985 entered into a partnership to establish a group of Centers for Molecular Biology in the Cardiovascular System. The goal was to recruit and train young scientists with medical training to apply molecular and cellular biology knowledge and techniques to cardiovascular problems.Six Centers have been awarded (three in 1986 and three in 1991), and a total of 110 trainees have been involved as of June 30, 1994. Of these trainees, 77 were recruited and trained by the 1986 Centers. As of June 1994, 88% of these trainees remained in academic medicine and 54% progressed to higher academic ranks; 79% published papers in science and 66% in molecular biology; and 36% obtained extramural funding for their work. On this basis, the 1986 trainees appear to be well on their way to becoming successful academic cardiologists.The AHA-Bugher Foundation Center program has produced a cadre of cardiovascular scientists who are applying molecular biology knowledge to both basic and clinical problems.
Industry, FDA Warm to “Adaptive” Trials
Authors: Bridget M. Kuehn
Journal: JAMA (2006)

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
Role of enteric bacteria in the pathogenesis of rheumatoid arthritis: evidence for antibodies to enterobacterial common antigens in rheumatoid sera and synovial fluids.
Authors: S Aoki, K Yoshikawa, T Yokoyama, T Nonogaki, S Iwasaki, T Mitsui, S Niwa
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To study antibodies to Escherichia coli O:14, which expresses large amounts of enterobacterial common antigen (ECA), and their corresponding antigen molecules in serum and synovial fluid samples from patients with rheumatoid arthritis (RA). METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure antibodies to heat killed E coli O:14 in serum and synovial fluid samples from patients with RA and control subjects including healthy donors and patients with osteoarthritis. ELISA was also used to perform absorption analyses of antibodies to E coli O:14 with several enteric bacteria and their lipopolysaccharide (LPS). In addition, antigenic molecules reacting with E coli O:14 antibodies from patients with RA were examined using immunoblot analysis and N-terminal amino acid analysis. RESULTS: Compared with control subjects, patients with RA showed significantly increased titres of antibodies against heat killed E coli O:14 in 33 of 83 serum samples (39.8%) and 38 of 58 joint fluid samples (65.5%). Absorption analyses with enteric bacteria and their LPS resulted in the reduction of antibody titres to heat killed E coli O:14 in serum and synovial fluid samples from the RA patients. In addition, immunoblot analysis of the samples from RA patients revealed not only a ladder-like banding pattern equivalent to ECA associated with LPS, but also two clear bands of bacterial outer membrane proteins of 35 kDa (Omp A) and 38 kDa (Omp C), having amino acid sequence homology with those of other Enterobacteriaceae. CONCLUSION: These results suggest that some patients with RA are sensitised to antigens common to Enterobacteriaceae, and this may prove relevant to the future development of immunotherapy for RA. Furthermore, this sensitisation to antigens found commonly in Enterobacteriaceae may have a key role in the pathogenesis of human RA similar to that described previously in our animal model.
Junior doctors deplore phasing of review body award Ministerial group on new deal should be recalled GPs will discuss their core services Patients get guidance on living wills
Authors: L. Beecham
Journal: BMJ (1996)

# Junior doctors deplore phasing of review body award {#article-title-2}

Representatives of junior hospital doctors have unanimously deplored the government's decision to phase the implementation of the 1996 award of the Review Body on Doctors' and Dentists' Remuneration. Senior registrars, registrars, and specialist registrars were awarded a 5.3% increase and senior house officers and house officers a 6.8% increase from 1 April but 1% has been withheld until 1 December. The higher award for junior grades was made partly to compensate for a reduction in the rates for class 3 additional duty hours of 2.5% to 50% of basic pay.

The Junior Doctors Committee welcomed the fact that the awards have partly addressed the relative deterioration in the pay of training grade doctors but at its recent meeting it also criticised the government for not funding the awards in full and insisting that they will have to be funded, in part, from local efficiency savings. “Hospitals will have to take our pay increases from patient care,” according to Dr Edwin Borman, an anaesthetic senior registrar in Birmingham. “It is quite wrong that the government is allowing hospitals to squeeze the service.”

The representative from the General Medical Services Committee, Dr Ian Banks, pointed to the differential in pay—as much as £7000—between the salary of general registrars and hospital registrars. The review body had not accepted that there was a recruitment crisis in general practice. Specialist registrars should have automatic increments.

The JDC also deplored “anything other than the automatic implementation” of the salaries of doctors in the new specialist registrar grade. The review body recommended …
Health Law and Policy: A Survival Guide to Medicolegal Issues for Practitioners
Authors: Marshall B. Kapp
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes4 April 2000Health Law and Policy: A Survival Guide to Medicolegal Issues for PractitionersMarshall B. Kapp, JD, MPHMarshall B. Kapp, JD, MPHWright State University School of Medicine, Dayton, Ohio. (Kapp)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-7-200004040-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Liang BA. 309 pages. Boston: Butterworth-Heinemann; 2000. $39.95. ISBN 0750671076. Order phone 800-366-2665.Field of medicine: Legal medicine.Format: Softcover book.Audience: Physicians from all specialties, other health care professionals, and administrators.Purpose: To provide health care professionals with basic information on contemporary legal issues so that they can better navigate the health care system and recognize and avoid potential adverse legal entanglements.Content: The first of four sections describes the legal system, malpractice, informed consent, medical records, and the provider-patient relationship. The second part outlines private and public programs and methods of paying for medical services, noting the legal ... Author, Article, and Disclosure InformationAffiliations: Wright State University School of Medicine, Dayton, Ohio. (Kapp) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 April 2000Volume 132, Issue 7Page: 604KeywordsHealth careHealth information technologyMedical servicesSoftware tools ePublished: 15 August 2000 Issue Published: 4 April 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PROTECTIVE INOCULATION AGAINST INFLUENZA
Authors: W. H. Wynn
Journal: BMJ (1920)

THE possibility of a recrudescence of influenza iand the distribution .ofvaccine by the Ministry of Health has caused much questioning, both by medical m-en and -the general publi, as to the advisability 'of prophylactic inioculation.Although the true value of vaccines for prophylaxis against epidemic influenza cannot be established until the morbidity of a large sample -of the population, inoculated before an outbreak, as compared with that in uninoculated controls, is -submittd to expert statistical treatment, yet we possess much useful informa- tion gained during the last epidemics.Until we know the -true cause of influenza, the use of a vaccine must necessarily.be empirical, but whatever the cause, there is little doubt that Pfeiffer's bacillus, and various strains of pneumococci and streptococci, are important secondary or coincident infecting agents,-and are responsible for the severe and fatal complications.Tihere is evidence that a vaccine composed of -these three organisms will not only diminish-.themortality and reduce the complications of the disease, but will also lessen the incidence of uncomplicated influenza.If this latter fact can be proved, it must be taken seriously intu account in any discussion upon the true virus of influenza.Most
Urinary Incontinence Associated With Metoclopramide
Authors: Julian Hasen
Journal: JAMA (1984)

To the Editor.—  Metoclopramide-induced urinary incontinence attributed to a possible relaxing effect of this drug on the urethral sphincter 1 betrays an astute observer with a good sense of intuition.  Indeed, a significant drop in maximum urethral closure pressure within two minutes of intravenous administration of thyroid-stimulating hormone (TSH)-releasing hormone lasting for ten minutes was recently described. 2   Since the effect of metoclopramide and TSH-releasing hormone on the pituitary is similar with regard to TSH and prolactin release, it is reasonable to suggest that an analogous situation exists in the urethral smooth muscle. Urodynamic studies might demonstrate such an effect for metoclopramide as well.
547. Improvement of Liver Gene Transfer by First and Third Generation Adenoviral Vectors
Authors: Julien S. Crettaz, Pedro Berraondo, Itsaso Mauleon, Laura Ochoa, Veijay Shankar, Miguel Barajas, Maider Zabala, Nico van Rooijen, Stefan Kochanek, Cheng Qian, Jesus Prieto, Ruben Hernandez-Alcoceba, Gloria Gonzalez-Aseguinolaza
Journal: Molecular Therapy (2005)

Recombinant adenoviruses are among the most extensively used vectors in gene therapy studies. To optimize adenovirus-mediated liver transduction we have studied the effect of the route of administration using first and third generation adenovirus vectors. We compared the local delivery of those vectors, using direct intrahepatic injection (IH), and the systemic administration via tail vein (IV). IH injection of first generation adenovirus resulted in a three-fold increase transgene expression when a high dose of virus was administered. More importantly when a relatively low dose of virus was used, IV administration resulted in no detectable protein expression while IH administration resulted in high levels of protein in serum. Significant differences in the kinetic and location of protein expression were observed depending on the route, IH injection resulted in a faster protein expression which localized to the site of injection, compared to widespread liver expression following IV administration. A 3 fold increase in the level of protein expression was also obtained after IH injection of a helper-dependent adenovirus expressing hIL-12 (HD-hIL12). Furthermore, IH injection using a HD-Ad carrying murine IL12 (HD-mIL12) correlated with the improvement of its antitumoral efficacy in a murine tumor model. Macrophage depletion experiments using clodronate loaded-liposomes showed that IH injection partially circumvent macrophage phagocytic activity. Interestingly, the administration of empty liposomes increases transgene expression without macrophage depletion regardless of the route of administration. In summary, our study describes two ways to improve liver transduction using adenovirus-based vectors: 1, direct liver injection of the adenovirus 2, administration of empty liposomes prior to virus injection.
An Inherited Disorder of Lymphocyte Apoptosis: The Autoimmune Lymphoproliferative Syndrome
Authors: Stephen E. Straus
Journal: Annals of Internal Medicine (1999)

The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. This syndrome arises early in childhood in persons who inherit mutations in genes that mediate apoptosis, or programmed cell death. The timely deletion of lymphocytes is a way to prevent their accumulation and the persistence of cells that can react against the body's own antigens. In ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and splenomegaly; the survival of normally uncommon "double-negative" CD3+ CD4 −CD8 −T cells; and the development of autoimmune disease. Most cases of ALPS involve heterozygous mutations in the lymphocyte surface protein Fas that impair a major apoptotic pathway. Detailed immunologic investigations of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype; this provides a rational explanation for the humoral autoimmunity typical of patients with ALPS. Prospective evaluations of 26 patients and their families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia. Defective apoptosis may also contribute to a heightened risk for lymphoma.
Complications of Malignancy
Authors: S. Nimubona, M. Bernard, P. Morice, G. Brassier, S. Caulet-Maugendre, B. Carsin, C. Meunier, T. Lamy
Journal: Journal of Clinical Oncology (2004)

underwent a laparotomy, ileocolectomy, ileostomy, and transverse colon mucous fistula.Intraoperative findings were consistent with a cecal adenocarcinoma that had perforated into the retroperitoneal soft tissues and into the peritoneal cavity.Pathologic evaluation showed a 9 cm poorly differentiated pT3N2M1 (Stage 4) adenocarcinoma.Despite aggressive support, the patient died from progressive septic shock within 24 hours.Increased risks to develop overwhelming infections or secondary cancers have been well documented for patients with Hodgkin's disease [1][2][3][4].Overwhelming sepsis, however, remains uncommon, and is primarily encountered after previous splenectomy [1,5]; it has been observed after doxorubicin, bleomycin, vinblastine, and dacarbazine therapy in the setting of recurrent disease [6].The infectious hazards after splenic irradiation are less clear, but have been postulated [7,8].An increased incidence of secondary neoplasms, both hematologic and solid, has been observed after all forms of therapy for Hodgkin's disease [9]; combination therapy leads to greater risks than monotherapy [10].Age greater than 40 at the time of the initial Hodgkin's diagnosis appears to be a risk factor [11,12].Secondary solid tumors are predominantly cancers of lung, breast, or colon, with an average latency period of 8 years [13].Our patient presented with metastatic colon cancer, and an infection with gas-forming organisms involving soft tissue at the perforated primary tumor and metastatic sites within the liver.There was no evidence for recurrence of lymphoma.Despite the unusual presentation, this case serves as an important reminder of the significance and possible complexity of neoplastic and infectious hazards that can be encountered in survivors of Hodgkin's disease.
Community Medicine: Success or Failure?
Authors: Willoughby Lathem
Journal: New England Journal of Medicine (1976)

Abstract The development of university-based community-medicine programs represents one of the most fundamental reforms in medical education in recent times. These programs have attempted to train and motivate students to undertake research and innovations in health service and health-care systems, and to provide service to those in need. Since community medicine is based upon the collective needs of population groups, its relevance, value and effectiveness as a teaching, research and service device in the United States must be seriously questioned unless the prevailing system of individualized care is fundamentally changed to one of collective and regionalized organization. Moreover, working with small population groups, university programs do not provide a large enough epidemiologic base to serve as models for this reform. In developing countries community medicine has proved to be ineffective when isolated from broader socioeconomic development, and should, as now constituted, be abandoned as an independent undertaking. (N Engl J Med 295:18–23, 1976)
A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR
Authors: Hiroki Torikai, Andreas Reik, Pei-Qi Liu, Yuanyue Zhou, Ling Zhang, Sourindra Maiti, Helen Huls, Jeffrey C. Miller, Partow Kebriaei, Brian Rabinovitch, Dean A. Lee, Richard E. Champlin, Chiara Bonini, Luigi Naldini, Edward J. Rebar, Philip D. Gregory, Michael C. Holmes, Laurence J. N. Cooper
Journal: Blood (2012)
Inhibition of Rat Cardiac Muscle Contraction and Mitochondrial Respiration by Endogenous Peroxynitrite Formation During Posthypoxic Reoxygenation
Authors: Yi -Wu Xie, Pawel M. Kaminski, Michael S. Wolin
Journal: Circulation Research (1998)

This study was designed to investigate the potential role of endogenous peroxynitrite (ONOO-) formation in the inhibition of cardiac muscle contractility and mitochondrial respiration during posthypoxic reoxygenation. Isometric contraction of isolated rat left ventricular posterior papillary muscle was virtually eliminated at the end of an exposure to 15 minutes of hypoxia and remained 40+/-5% depressed an hour after the reintroduction of O2. O2 uptake by rat left ventricular cardiac muscle, measured by a Clark-type O2 electrode, was also inhibited by 24+/-2% at 10 minutes after reoxygenation. The inhibition of contractility and respiration during posthypoxic reoxygenation was markedly attenuated by the NO synthase inhibitor nitro-L-arginine, exogenous superoxide dismutase, and the ONOO- scavenger urate but not by the hydroxyl radical scavenger mannitol. Generation of ONOO- with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) plus the superoxide-releasing agent pyrogallol caused an irreversible inhibition of cardiac contractile and respiratory function. Unlike ONOO-, exogenous (SNAP) and endogenous (bradykinin) sources of NO inhibited contractility in a reversible manner. Under conditions of comparable amounts of respiratory inhibition in unstimulated incubated muscle, the NO-dependent agents and the mitochondrial antagonist NaCN produced a smaller degree of suppression of contractility compared with ONOO- and posthypoxic reoxygenation. These results are consistent with a contributing role for endogenous ONOO- formation in the inhibition of cardiac muscle contractility and mitochondrial respiration during posthypoxic reoxygenation.