tbuckley/cabot-search huggingface dataset:
Abstract 4177: Copy number variations of FGFR1 and 2 in NSCLC; implications for targeted drug development
Authors: Marcus Otte, Kanchev Ivan, Elvira Stacher, Michael Sharp, John D. Alvarez, Helmut Popper, Hans Winkler, Suso Platero
Journal: Cancer Research (2011)

Abstract NSCLC is the cancer with highest death rate; it is typically diagnosed at a late stage and has limited therapeutic options. FGFR signaling is a potential oncogenic driver in many cancers, including NSCLC. In this study we evaluated the copy number variations (CNVs) of FGFR1 and FGFR2 by dual color FISH in specimens from 139 NSCLC patients (78 SCC, 46 ADC, 15 other). CNVs were observed for both FGF receptors. However, FGFR1 was more frequently affected by CNV than FGFR2 (45% vs. 17%). Only a small fraction of patients exhibited CNV of both receptors. In general, the level of gene amplification was higher for FGFR1 as compared with FGFR2. Interestingly, FGFR2 CNV exhibited a high degree of intra-tumor heterogeneity. FGFR1 gene dose elevations were observed due to gene locus amplification (27%) as well as polysomy of chromosome 8 (17%). The degree of gene locus amplification was classified from low (gene ratio 1.5 – 2.5) to high (&amp;gt;4.5). An analysis of the two most common histologies (i.e. Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC)) indicated that gene locus amplifications were more frequent in SCC (38%) as compared with ADC (7%), while polysomy of chromosome 8 was observed at similar rates (18-19%). Lack of FGFR1 rearrangements was confirmed using a break-apart FISH probe. FGFR2 gene dose elevations show gene locus amplifications and polysomy of chromosome 10. Locus amplifications of FGFR2 were observed in 11% of SCC, but were not found in ADC. Similar rates for polysomy of FGFR1were observed in SCC (7%) and ADC (5%). Overall, gene dose elevation of FGFR1 and FGFR2 were found more frequently in SCC. Of higher relevance is the fraction of patients with gene dose elevation due to gene locus amplification. Approximately 40% of the SCC patients possess gene locus amplification of at least one of the two probed FGF-receptors. However, only ∼9% of the SCC patients have both loci amplified. In conclusion here we present for the first time evidence for a potential genetic addiction of NSCLC, specifically on FGFR1 gene locus amplification. Therefore targeting FGFR in combination with proper patient stratification, may be an attractive opportunity to develop improved clinical options for treatment of NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4177. doi:10.1158/1538-7445.AM2011-4177
Rates of admission to hospital for asthma
Authors: S J Hyndman, D R R Williams, S L Merrill, J M Lipscombe, C R Palmer
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To describe trends in hospital admission rates for asthma in England and Wales (1976-85), the East Anglian region (from 1976 to 1991- 2), and Wales (1980-90). <b>Design</b>: Descriptive study. <b>Setting</b>: Hospitals in England and Wales; hospitals in the East Anglian Regional Health Authority; hospitals in Wales. <b>Main outcome measures</b>: Hospital admissions for asthma as principal diagnosis in England and Wales (Hospital In-patient Enquiry, 1976-85), for the East Anglian region (Hospital In-patient Enquiry, 1976-7; Hospital Activity Analysis, 1978-86; Regional Information System, 1987-8 to 1991-2), and for Wales (Hospital Activity Analysis, 1980-90). Results - Rates for England and Wales as a whole showed a steady upward trend throughout the period examined. Rates in East Anglia, though they were similar to the national trends in the early years, showed a peak in 1985 (for males and females) with some indication of a decline in rates thereafter. Rates for Wales showed an upward trend until 1988 (for both males and females) after which they showed a decline. <b>Conclusions</b>: Interpretation of the East Anglian trends is made more difficult by the change in England in 1987 of the system for the collection of hospital admission data. The fact that the rates for the East Anglian region seem to decline before this change and other considerations suggest that the observed trends, although partly reflecting the disruption of the coding during the changeover in systems, may not be entirely artefactual. The possible roles of diagnostic transfer and changes in the delivery of care, asthma treatment, admission and readmission policies, and the severity and prevalence of asthma in changing admission rates are considered. The changing trends in admission rates for East Anglia and Wales reflect recently published trends for mortality from asthma in England.
Rapid Evaluation of Acute Abdominal Pain by Hepatobiliary Scanning
Authors: John E. Freitas
Journal: JAMA (1980)

One hundred eighty-six patients with suspected acute cholecystitis (AC) underwent radionuclide hepatobiliary imaging with technetium Tc 99m iprofenin to assess the ability of this tracer to detect AC. After intravenous injection of 5 to 10 mCi of this agent, 500,000 count anterior images were obtained at ten-minute intervals for 60 minutes. An abnormal hepatobiliary scan (HBS) diagnostic of AC was defined as one in which the common bile duct, but not the gallbladder, visualized within one hour of tracer administration. In this series, the sensitivity and specificity for HBS in the detection of AC were 97% and 87%, respectively. The hepatobiliary scan should be the procedure of choice for the rapid detection of AC. It is simple, rapid, and safe to perform, enabling a diagnosis to be established within one hour. (<i>JAMA</i>244:1585-1587, 1980)
Intratumoral Immune Cell Infiltrates, FoxP3, and Indoleamine 2,3-Dioxygenase in Patients with Melanoma Undergoing CTLA4 Blockade
Authors: Antoni Ribas, Begoña Comin-Anduix, James S. Economou, Timothy R. Donahue, Pilar de la Rocha, Lilah F. Morris, Jason Jalil, Vivian B. Dissette, Itsushi Peter Shintaku, John A. Glaspy, Jesus Gomez-Navarro, Alistair J. Cochran
Journal: Clinical Cancer Research (2008)

Abstract Purpose: CTL-associated antigen 4 (CTLA4)-blocking monoclonal antibodies induce long-term regression of metastatic melanoma in some patients, but the exact mechanism is unknown. In this study, biopsies of selected accessible tumor lesions from patients treated with tremelimumab were examined to further elucidate the mechanism of its antitumor activity. Experimental Design: Fifteen tumor biopsies from 7 patients who had been treated with tremelimumab (CP-675,206) were collected. Samples were analyzed for melanoma markers, immune cell subset markers, the presence of the T regulatory-specific transcription factor FoxP3 and the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). Results: Clinically responding lesions had diffuse intratumoral infiltrates of CD8+ T cells that were markedly increased in cases where comparison with a baseline biopsy was available. Nonregressing lesions had sparse, patchy CD8+ intratumoral infiltrates. Patients with regressing lesions had an increased frequency of CD8+ cells with or without a concomitant increase in CD4+ cells. Two of 3 responding patients with paired samples showed a slight increase in the number of FoxP3+ cells in the postdosing biopsies. In patients with regressing lesions who had paired samples, the intensity of IDO staining in macrophages and/or melanoma cells showed no clear pattern of change postdosing. Conclusions: Administration of tremelimumab was associated with massive intratumoral infiltrates of CD8+ CTLs in patients with regressing tumors but had varying effects on intratumoral infiltrates of CD4+ and FoxP3+ cells or intratumoral expression of IDO.
386. Chromosomal Integration Sites of Double-Stranded Linear DNA in Mouse ES Cells
Authors: Fumi Ohbayashi, Ko Mitani
Journal: Molecular Therapy (2006)

In gene therapy approaches for inherited diseases, efficient transduction of target cells as well as stable maintenance of the therapeutic gene are required. Major viral vectors currently in use for efficient chromosomal integration in gene therapy include retroviral, lentiviral and adeno-associated viral (AAV) vectors. Recent large-scale analysis of chromosomal integration sites revealed the potential risk of insertional mutagenesis caused by these vectors. While retroviral and lentiviral vectors tend to integrate into transcription units, DNA viral vectors, such as AAV and adenoviral vectors, reportedly have no such strong preference, at least in tissue culture cells.
Differentiation status of rat enterocytes after intestinal adaptation to jejunoileal bypass.
Authors: V Albert, G P Young
Journal: Gut (1992)

The differentiation status of epithelial cells in intestinal adaptation remains unclear. To determine whether enterocytes reach optimum maturity following adaptation after 85% shortening of the rat gut by jejunoileal bypass surgery, activities of two brush border enzymatic markers of differentiation, alkaline phosphatase and sucrase, were examined in subpopulations of epithelial cells isolated sequentially from the villus/crypt axis of normal (sham operated) and hyperplastic mucosa. In jejunal villi, adaptational hyperplasia was associated with an increase in total epithelial alkaline phosphatase, but not total sucrase, activity; alkaline phosphatase activity increased most obviously in cells at the 11-50% position (from the tip) on villi. In hyperplastic ileal villi, total alkaline phosphatase activity fell, although sucrase activity did not change significantly. Specific activity (per mg protein) of sucrase on jejunal villus epithelium was reduced by the adaptational changes to bypass; alkaline phosphatase specific activity remained unchanged. In the ileum, despite adaptational changes to bypass, there was no increase in the normally low specific activities of sucrase and alkaline phosphatase. Bypass surgery did not change the major site of expression of either enzyme on jejunal or ileal villi. In conclusion, enzymatic markers of functional differentiation are not all equally affected by adaptational hyperplasia. Hypertrophy of villi and increased cell proliferation seen in jejunum remaining exposed to luminal contents resulted in an increase in the alkaline phosphatase but not the sucrase content. This is not, therefore, the result of a simple immaturity of villus cells. Morphological adaptation in the ileum, however, is not accompanied by adaptation of brush border enzyme markers of differentiation, confirming a functional immaturity of these cells. Strategies for increasing the expression of these markers may have clinical value.
Use of electronic medical records expands in the US, but some hospitals are trailing
Authors: M. McCarthy
Journal: BMJ (2013)

US hospitals and physicians seem to be responding to federal financial incentives and accelerating their adoption of electronic health records, according to two new studies published online by the journal Health Affairs .

In 2009, Congress passed the Health Information and Technology Act, which authorized nearly $30bn (£10bn; €23bn) to promote the adoption of electronic health records.

The law created financial bonuses as well as penalties to induce doctors and hospitals to adopt systems that met specific criteria for “meaningful use,” which gradually become more demanding over a period of years.

These criteria require the systems to have capabilities that have been shown to improve the efficiency and quality of care, such as computerized order entry, electronic prescribing, and automatic reminders to help doctors follow clinical guidelines.

The first study—led by Catherine DesRoches, a senior scientist at Mathematica Policy Research in Cambridge, Massachusetts—looked at the adoption of …
Varicella Vaccine Licensing in 18 to 24 Months?
Authors: Charles Marwick
Journal: JAMA (1987)

PRELICENSING STUDIES with the experimental live-virus chickenpox vaccine had been going well. The manufacturer, Merck Sharp &amp; Dohme, West Point, Pa, decided to start making the vaccine in quantity. The first production lots of any new unlicensed vaccine also are for investigational use, including testing in additional human trials. At this point, a problem emerged. In the volunteers with leukemia who were given this production vaccine, there were more frequent vesicular lesions when compared with patients with leukemia who had received the research vaccine. The difference was statistically significant. Even though there was no increase in adverse effects in normal subjects and no serious reactions occurred even in subjects with leukemia, Merck stopped trials with the vaccine while the problem was investigated. That was in January 1986. Almost 18 months later, after extensive review of all the clinical data and of the steps involved in making both the earlier research
Change, we must – for the better
Authors: JK Anand, JW Myles
Journal: Journal of the Royal Society of Medicine (2009)

Your Editorial1 and the comments in the Podium2 together with the rather sad responses by some patients and some doctors reported in the same issue (December 2008) stimulated us to put forward the views of a couple of doctors of an earlier generation.

Like Professor Aziz Sheikh we see the need to re-kindle the human side of medicine, as so poetically expounded by William R Phillips, while at the same time, like Professor Antonio Vaz Carneiro, never forgetting for one moment that effective treatment must always be based on the best available evidence.

Perhaps a change worth considering would be setting up, by means of donations, of one or two free hospitals treating all comers and staffed by men and women primarily motivated by faith, whether religious or humanitarian. Such institutions might help to draw together, as donors, hospital workers and as patients, members of various communities and improve their understanding of and respect for each other. At the same time such institutions could set compassionate holistic standards of care to which NHS institutions might be stimulated to aspire.
Role of comorbid conditions in asthma hospitalizations in the south of France
Authors: C. Aubas, A. Bourdin, P. Aubas, A. S. Gamez, L. Halimi, I. Vachier, N. Malafaye, P. Chanez, N. Molinari
Journal: Allergy (2013)

Abstract Background Reasons for asthma hospitalizations are dynamic and complex. Comorbid conditions are important contributors to most chronic diseases today. We aim to characterize and describe risk factors associated with hospitalizations due to asthma in the Languedoc‐Roussillon region (France) in 2009. Methods Programme de Médicalisation des Systèmes d'Information ( PMSI ) data records from 2009 were sorted using selected International Classification of Diseases ( ICD 10) codes eliciting three groups of asthma hospitalizations according to acute severity. All available data including demographics, comorbid conditions, past hospitalizations either related or unrelated to asthma, seasonality and distance to medical facilities were used to compare the subjects within the three groups. Results One thousand two hundred and eighty‐nine hospitalizations due to asthma exacerbation were found, concerning 1122 patients. We observed significant differences within the groups, using univariate analysis, concerning duration of hospitalizations (mean ± SD, 4.9 ± 5.9 days vs 6.4 ± 6.8 vs 15.8 ± 16.8, P &lt; 0.001), deaths (percentage, 0.03% vs 1.50% vs 9.20%, P &lt; 0.001) and numbers of comorbid conditions (0.80 ± 0.95 vs 0.75 ± 0.97 vs 1.74 ± 1.36, P &lt; 0.001). Recurrent admissions for asthma during the period 2006–2008 were significantly more frequent in the more severe group (1.93 ± 3.91 vs 2.56 ± 4.47 vs 2.81 ± 3.97, P = 0.006). In the multivariate model, age and number of comorbid conditions were independently associated with severe hospitalizations and deaths. Conclusions Asthma hospitalizations can be appropriately assessed using PMSI coding databases. In this study, age and the presence of comorbid conditions are the major risk factors for asthma hospitalizations and deaths.
In-frame TCR δ gene rearrangements play a critical role in the αβ/γδ T cell lineage decision
Authors: Ferenc Livak, Howard T. Petrie, I.Nicholas Crisps, David G. Schatz
Journal: Immunity (1995)

Using a quantitative multiprobe Southern blot analysis, we demonstrate the surprising result that a significant proportion of alpha beta T cells and thymocytes retain T cell receptor delta locus sequences. A substantial portion of the retained delta locus is in a fully V-to-D-to-J rearranged configuration and 20% of these delta rearrangements are functional, significantly less than the 33% predicted for random gene rearrangements. Our observations are in conflict with the idea that alpha beta and gamma delta T cells derive from distinct precursors and suggest that commitment of a common precursor to the gamma delta lineage depends upon expression of a gamma delta T cell receptor. We propose that the intrathymic T cell lineage decision is determined by a competition between the production of functional gamma delta and beta-pre-T cell receptor complexes.
May I take this opportunity ...
Authors: T. Greenhalgh
Journal: BMJ (1999)

It's the conference season in my discipline. I am growing weary of the 5 30 am alarm calls and crowded train journeys to some or other grubby suburban institution whose logo has always given the impression of a centre of international excellence. I am looking for a taxonomy for my growing collection of misspelt name badges, giveaway pencils, and plastic delegate bags. And I am developing a list of pet aversions which includes taxi drivers, contract caterers, women with clipboards who say they …
Genomics and Public Health Research
Authors: Muin J. Khoury, Marta Gwinn, M. Scott Bowen
Journal: JAMA (2007)

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
Sleeping Beauty II: Grief, Bereavement and the Family in Memorial Photography: American and European Traditions
Authors: R. E. Peschel
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
What's Legal? What's Moral? What's the Difference? A Guide for Teaching Residents
Authors: Christy A. Rentmeester
Journal: The American Journal of Bioethics (2006)

Click to increase image sizeClick to decrease image size Notes 1. It's useful to note one distinction between members of hospital counsel and risk managers. Often, risk managers are trained as healthcare professionals; they help educate staff about practices (e.g., documentation) within an organization that have been considered by members of hospital counsel to be efficient ways of ensuring that individual practitioners can easily and routinely practice in ways that comply with legal standards. Generally, risk managers are not specifically trained in law; hospital counselors are. 2. For interesting legal, medical and humanist discussions of liminality in healthcare, see CitationChambers (2006), CitationKirschner (2006) and CitationWatson (2006). 3. There does not appear to be any good reason why palliation can not also be aggressive.
Central Circulatory Changes Accompanying Mitral Commissurotomy
Authors: HAROLD G. RICHMAN, J. BRADLEY LONG, ELLIOT RAPAPORT
Journal: Circulation (1960)

The flow-pressure relationships within the pulmonary circuit and left side of the heart were measured in 24 patients immediately before and just after mitral commissurotomy. The diastolic pressure gradient across the mitral valve was decreased in all cases, but was rarely obliterated completely. No significant change occurred in cardiac output; a shorter ventricular filling period and a consequent increase in mitral valve flow per unit of filling time was consistently observed. A decrease in mean pulmonary artery pressure generally occurred with valve fracture, but it was almost always less than the decrease in left atrial pressure. The result was an immediate postoperative increase in the pressure gradient and in the calculated resistance across the pulmonary circuit. These observations suggest that the reduction in left atrial pressure following mitral commissurotomy has no immediate effect on pulmonary vasomotor tone.
Remarks on Suprapubic and Lateral Lithotomy and on Litholapaxy
Authors: J. A. Cunningham
Journal: BMJ (1891)

ing of DJecember 16th.His friends would not allow a postmortem examination.Litholapa.xy in Male ('hildren.-When, in 1885, Keegani first slhowed that lBigelow's operation was capable of successful ex- tension to the case of male children, I lost no time in procur- ing the necessary instruments, and, applying tle operation to such cases.ifn two papers 2 I placed before the profession full details of 49 cases of litholapaxy undertaken by me in male childrein, or boys below tlle age of puberty.Since then 67 males of 1.5 years and under, suffering from stone, have come under treatment, anid in 66 of tlhese I lhave performed litholapaxy-in all, wvith complete success.In only one instance was it, necessary to lhave recourse to litliotomy (suprapubic).The greater my experience of litliolapaxy amongst male children becomes, the more I am fasciniated by this operation.Thlough the average number of days such cases were kept inl hospital was 52 as a rule, these little patients may be seen playing about the (lay after the opera-