tbuckley/cabot-search huggingface dataset:
Carvedilol, Metoprolol, and Insulin Resistance—Reply
Authors: David S. Bell, George L. Bakris
Journal: JAMA (2005)

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
Abstract 02: Lifetime Risk of Lower Extremity Peripheral Artery Disease in the US
Authors: Kunihiro Matsushita, Yingying Sang, Shoshana Ballew, Eric K Chow, Morgan Grams, Elizabeth Selvin, Alan T Hirsch, Josef Coresh
Journal: Circulation (2015)

Background:  Prevalence provides information about the burden of disease in the population but does not capture individuals’ risk over time. In contrast, lifetime risk is a useful measure of long-term disease incidence in an individual and is underscored for coronary disease and stroke in the AHA/ACC 2013 guidelines. However, there are no available estimates of lifetime risk of lower extremity peripheral artery disease (PAD), despite its impact on prognosis, leg amputation, and physical function.   Methods:  With an established method for lifetime risk estimation used in other fields (e.g., kidney disease), we estimated national average probability of developing PAD, defined as an ankle-brachial index (ABI)    Results:  In an 80-year horizon, lifetime risk of PAD was similar between sexes but 1.5-fold higher in blacks compared to whites (35.6% for black women, 30.6% for black men, 22.5% for white women, and 19.4% for white men) (Figure). From another perspective, 10% of blacks and whites develop PAD by the age of 60 years and 70 years, respectively. The remaining lifetime risk at ages of 65 (for those free of PAD until this age) through 80 years was 29.6% in black women, 28.0% in black men, 17.9% in white women, and 16.5% in white men.   Conclusion:  In the US, 1 in 3 blacks and 1 in 5 whites will experience lower extremity PAD during their life course. This is the first national estimate of lifetime risk for PAD and should help inform risk-centered screening and prevention strategies. Our results suggest that race is a critical factor in PAD risk, a factor not taken into account for ABI screening in the current clinical guidelines.
Colon Cancer Screening Guidelines Stress Initial Test's Importance
Authors: Mike Mitka
Journal: JAMA (2003)

THE AUTHORS OF NEW GUIDELINES for colorectal cancer screening tweaked existing recommendations while stressing the importance of initial screenings for people aged 50 years or older. The initial screen is especially important because it detects the largest, most dangerous polyps, which can be removed through a polypectomy, according to the American Gastroenterological Association. It also helps get patients in the habit of screening, thus improving the chances of early detection of colorectal cancer—a key factor in surviving this malignancy. The guidelines, by the US Multisociety Task Force on Colorectal Cancer, were published in February (Gastroenterology. 2003;124:544-560). This is an update of the original 1997 guidelines, prepared by a panel convened by the US Agency for Health Care Policy and Research.
Abstract P5-02-12: Concordance between semiquantitative immunohistochemical assay and oncotype DX RT-PCR assay for estrogen and progesterone receptors
Authors: Patricia Novas, Elena Galve, Sara Fernández, Maria Ángeles Sala, Alberto Arévalo, Juan Arango, Borja López de San Vicente, Seila Fernández, Ane Zumárraga, Purificación Martínez del Prado
Journal: Cancer Research (2015)

Abstract Introduction: Estrogen receptor (ER) and progesterone receptor (PR) expression are generally determined by semiquantitative immunohistochemistry (IHC) as recommended in the clinical practice guidelines of the American Society of Clinical Oncologists. This method may be subject to variability because of differences in fixation, ER antibody clones, as well as to immunostain interpretation and use of arbitrary cut-off points. Materials and methods: We identified 72 breast cancer cases at Basurto University Hospital from 1 September 2012 to 31 May 2014 that have been analyzed by Oncotype DX with reporting on ER/PR expression levels by RT-PCR (Genomic Health Inc, Redwood City, CA). According to the company’s report, a tumor is considered as ER positive with expression units of &amp;gt;=6.5 and PR positive with expression units of &amp;gt;=5.5. Oncotype DX is a commercial assay that predicts tumor recurrence in node-negative ER-positive breast cancers. It is a reverse transcription-polymerase chain reaction (RT-PCR) based assay that analyzes the expression of 21 genes (16 cancer-related and 5 control genes) to provide a distant disease recurrence score ranging from 0 to 100. At our institution, hormone receptors by IHC were analyzed on corresponding surgery breast specimens at the time of initial diagnosis. They were evaluated by IHC on formalin-fixed paraffin-embedded tissue, between 8-72 hours. ER was assessed using Roche antibody clone SP1 and PR was assessed using antibody clone 1E2. Percentage of positive nuclei was determined by visual microscopic estimation: &amp;lt;1 negative and ≥1 positive. We compared our semiquantitative method of reporting ER and PR status based on IHC to the RT-PCR hormone receptor results from Genomic Health. Results: There was 100% concordance between IHC and the RT-PCR assay for estrogen receptor status. PR findings between IHC and Oncotype Dx revealed a lower concordance (82%) than for ER. RT-PCR was negative in 10 (14%) cases in which IHC was positive. Pearson correlation coefficient for PR was 0.313. Although our results demonstrated high concordance between IHQ and Oncotype Dx for ER, our data showed poor concordance for PR. Citation Format: Patricia Novas, Elena Galve, Sara Fernández, Maria Ángeles Sala, Alberto Arévalo, Juan Arango, Borja López de San Vicente, Seila Fernández, Ane Zumárraga, Purificación Martínez del Prado. Concordance between semiquantitative immunohistochemical assay and oncotype DX RT-PCR assay for estrogen and progesterone receptors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-12.
Abstract ES2-3: Management of metastatic HER2 positive disease: optimizing current therapies and an overview of new agents in development
Authors: Ian Krop
Journal: Cancer Research (2015)

Abstract Amplification of the HER2/neu gene occurs in approximately 20% of invasive breast cancers and is associated with aggressive clinical behavior. The development of HER2-targeted therapies, including trastuzumab, lapatinib, pertuzumab and trastuzumab emtansine (T-DM1) has revolutionized the treatment of this disease, leading to dramatic improvements in clinical outcomes. Given these improvements, the goals in treating patients with advanced HER2-positive breast cancer are to both extend survival as well as to minimize toxicities of therapy. In patients with newly diagnosed metastatic breast cancer, pertuzumab, in combination with trastuzumab and docetaxel, markedly improves survival and only mildly increases toxicity compared to trastuzumab and docetaxel. Pertuzumab, trastuzumab, and a taxane should thus be considered the standard of care for most patients in the first line setting. In the second line setting, the antibody-drug conjugate T-DM1is the standard of care as it is associated with longer survival and less toxicity than capecitabine and lapatinib. In 3rd and later lines of therapy, continuation of HER2-directed therapy is important, but there are no definitive data that a particular regimen (e.g. trastuzumab + chemotherapy, lapatinib + chemotherapy, trastuzumab + lapatinib) is superior in this setting. Thus decisions regarding choice of therapy should be guided by patients' preferences regarding toxicity profiles and route of administration. Although HER2-directed therapy has improved outcomes, resistance to these agents eventually develops in almost all patients. CNS metastases represent one increasingly common manifestation of treatment resistance in HER2-positive cancers. Understanding mechanisms of resistance and development of novel agents to overcome this resistance is critical. A multitude of agents designed to overcome resistance are currently being evaluated in the clinic including PI3-kinase inhibitors, more potent tyrosine kinase inhibitors, new antibody-drug conjugates, and novel immunotherapies. In addition, studies evaluating the genomic alterations present in metastatic HER2-positive cancer tissue are beginning to provide clues as to the mechanisms of resistance present in treatment refractory disease. It is possible that with continued improvements in therapies and a better understanding of molecular resistance mechanisms, mortality associated with metastatic HER2-positive breast cancer can be largely eliminated. Citation Format: Ian Krop. Management of metastatic HER2 positive disease: optimizing current therapies and an overview of new agents in development [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES2-3.
Abstract 492: Molecular Determinants of Ca2+-Handling Abnormalities Underlying Contractile Dysfunction in Dilated versus Fibrillating Goat Atria
Authors: Maura Greiser, Hans-Ruprecht Neuberger, Sunniva de Haan, Erik Harks, Ali El-Armouche, Sander Verheule, Ursula Ravens, Stanley Nattel, Maurits Allessie, Dobromir Dobrev, Ulrich Schotten
Journal: Circulation (2007)

Background: Atrial dilatation (AD) promotes atrial fibrillation (AF), and both cause dysfunctional atrial contractile remodeling. The molecular mechanisms underlying atrial contractile remodeling a...
Abstract 683: Sensitizing tumors to pro-oxidant therapy by inhibiting gamma-glutamyl transpeptidase
Authors: Marie H. Hanigan, Nancy Wakeham, Stephanie Wickham, Simon S. Terzyan
Journal: Cancer Research (2014)

Abstract We have reported that 73% of ovarian tumors express the cell surface enzyme gamma-glutamyl transpeptidase (GGT). Clinical studies have shown a poorer prognosis for ovarian tumors that are GGT-positive compared to GGT-negative tumors. GGT-positive tumors are able to use the glutathione in the interstitial fluid as an additional source of cysteine, the limiting component of intracellular glutathione synthesis in tumors. The concentration of cysteine/cystine in standard tissue culture media is more than 3 times the concentration in interstitial fluid. In this study we show that in studies of cultured cells, the high concentration of cysteine in tissue culture media obscured the role of GGT expression in drug resistance. However, culturing human ovarian tumor cells in tissue culture media containing physiological concentrations of cystine and glutathione demonstrated that the supply of cysteine/cystine regulates intracellular glutathione concentrations. In these studies, inhibition of GGT blocked the use of extracellular glutathione as a source of cysteine and sensitized the tumors to cisplatin, carboplatin and melphalan. Inhibiting GGT in patients would also inhibit GGT in the kidney resulting in the excretion of glutathione in the urine and depletion of cysteine from serum and interstitial fluid. As a result, inhibition of GGT in patients would sensitize both GGT-positive and GGT-negative tumors to pro-oxidant chemotherapy. Clinical application of this therapeutic strategy is limited by the fact that most inhibitors of GGT are glutamate analogs and too toxic for use in humans. We discovered a non-glutamate analog that is an uncompetitive inhibitor of GGT, and are developing more potent, non-toxic GGT inhibitors. We recently published the crystal structure of human GGT. We have now also solved the structure of the substrate-bound enzyme, the form of the enzyme to which our uncompetitive inhibitors bind. Using structure-based drug design and our physiologically relevant tissue culture system we are designing new GGT inhibitors and evaluating them for their ability to sensitize tumors to chemotherapy regimens used in the clinic. Supported by an Institutional Development Award (IDeA) from the National Institutes of Health under grant P20GM103640. Citation Format: Marie H. Hanigan, Nancy Wakeham, Stephanie Wickham, Simon S. Terzyan. Sensitizing tumors to pro-oxidant therapy by inhibiting gamma-glutamyl transpeptidase. [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 683. doi:10.1158/1538-7445.AM2014-683
Nurse led pilot schemes succeed despite obstacles
Authors: Jacqui Wise
Journal: BMJ (2001)

Nurse led pilot schemes have achieved a great deal despite hostility from doctors and many bureaucratic obstacles, a report from the King's Fund, an independent health care charity in London, has concluded.

In 1998 nine nurse led sites were launched in England as part of the first wave of personal medical services pilots. The nine pilots were designed to maximise the use of nursing skills and to allow nurses to exercise leadership within the primary care team. Many of the pilots aimed to serve vulnerable populations often poorly served by general practice, such as refugees or homeless people.

Five pilots were managed by community NHS trusts, two by existing GP …
Paediatric pathology service close to collapse after Alder Hey
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

Women who miscarry or lose a baby shortly after birth but are refusing to allow a postmortem examination to be carried out are missing out on vital information that could help them to have a healthy baby, doctors have warned.

Public confidence in paediatric pathology has plummeted in the aftermath of the retained organ affair at Alder Hey Children's Hospital in Liverpool, with the specialty now …
Abstract 742: Antitumor activity of Trametinib, a MEK1/2 inhibitor, in malignant pleural mesothelioma cells <i>in vitro</i>
Authors: Hiroyuki Cho, Seiji Matsumoto, Yoshiko Fujita, Ayumi Kuroda, Masaki Hashimoto, Teruhisa Takuwa, Toshi Menju, Makoto Sonobe, Nobuyuki Kondo, Hiroshi Date, Seiki Hasegawa
Journal: Cancer Research (2014)

Abstract Introducion: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy and there is no approved targeted therapy. The MAPK pathway plays critical roles in the regulation of cell proliferation, growth, differentiation, and survival in multiple solid tumors, including MPM. Trametinib, a selective MEK inhibitor, have a survival benefit in patients with V600 BRAF-mutant metastatic melanoma. FDA approved Trametinib for these patients in May 2013. The effect of Trametinib in MPM cells has not been well studied. Purpose: We examined the effects of Trametinib in MPM cells in vitro. Methods: To examine the effect of Trametinib on the proliferation of MPM cells, we performed cell proliferation assay using four MPM cell lines, NCI-H2452, NCI-H226, NCI-H2052 and MSTO-211H. To examine the effect of Trametinib on intracellular signaling, we performed Western blot analysis in NCI-H226 cell line. Results: Trametinib exhibited potent antiproliferative activity in all four MPM cell lines with IC50 values ranging from 0.5 μM to 44 μM. Trametinib blocked the phosphorylation of ERK until 72 hours and decreased the expression of CD44 in a dose-dependent manner. In addition, the expression of CD44 was inhibited (48-72 hours) after the suppression of ERK phosphorylation by Trametinib. Conclusions: Our results suggest that Trametinib is a promising therapeutic agent for MPM. Citation Format: Hiroyuki Cho, Seiji Matsumoto, Yoshiko Fujita, Ayumi Kuroda, Masaki Hashimoto, Teruhisa Takuwa, Toshi Menju, Makoto Sonobe, Nobuyuki Kondo, Hiroshi Date, Seiki Hasegawa. Antitumor activity of Trametinib, a MEK1/2 inhibitor, in malignant pleural mesothelioma cells in vitro. [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 742. doi:10.1158/1538-7445.AM2014-742
Detection of early lung cancer
Authors: S. Porter JC, Spiro
Journal: Thorax (2000)

Background.The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low-radiation-dose computed tomography (low-dose CT) in people at high risk of lung cancer.We report the baseline experience.Methods.ELCAP has enrolled 1000 symptom-free volunteers, aged 60 years or older, with at least 10 pack-years of cigarette smoking and no previous cancer, who were medically fit to undergo thoracic surgery.After a structured interview and informed consent, chest radiographs and low-dose CT were done for each participant.The diagnostic investigation of screen-detected non-calcified pulmonary nodules was guided by ELCAP recommendations, which included short-term high-resolution CT follow-up for the smallest non-calcified nodules.Findings.Noncalcified nodules were detected in 233 (23% [95% CI 21-26]) participants by low-dose CT at baseline, compared with 68 (7% [5-9]) by chest radiography.Malignant disease was detected in 27 (2.7% [1.8-3.8]) by CT and seven (0.7% [0.3-1.3]) by chest radiography, and stage I malignant disease in 23 (2.3% [1.5-3.3]) and four (0.4% [0.1-0.9]),respectively.Of the 27 CT-detected cancers, 26 were resectable.Biopsies were done on 28 of the 233 participants with non-calcified nodules; 27 had malignant noncalcified nodules and one had a benign nodule.Another three individuals underwent biopsy against the ELCAP recommendations; all had benign non-calcified nodules.No participant had thoracotomy for a benign nodule.Interpretation.Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage.Although false-positive CT results are common, they can be managed with little use of invasive diagnostic procedures.
The Symptoms of Dissecting Aneurysm of the Aorta
Authors: Leslie T. Gager
Journal: Annals of Internal Medicine (1929)

Article1 January 1929The Symptoms of Dissecting Aneurysm of the AortaLESLIE T. GAGER, M.D.LESLIE T. GAGER, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-7-658 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDissecting aneurysm of the aorta presents a clinical paradox: the anatomical changes which are thus produced are easily among the most striking lesions of the circulatory system, and yet the diagnosis has been made during life only with the utmost rarity.Interesting myself in the subject after my own failure to recognize an outspoken example, a survey of the literature, from Morgagni (1) to the present year, discloses a total of 382 case reports of dissecting aortic aneurysm, with mention, but not the data, of at least 30 additional cases. Dissections within the heart, or those confined to the smaller...References(1) MORGAGNI : De Sedibus, Venice, 1761. Epist. 58, no. 14. Google Scholar(2) SWAINE : With Latham, Trans. Path. Soc. Lond., 1855-56, vii:106. Google Scholar(3) WYSS : Arch. der Heilkunde, 1869, p. 490. Google Scholar(4) MAGER : Zeitschr, f. Heilkunde (Path. Anat.), 1903, xxiv:323. Google Scholar(5) DAVYGATES : Brit. M. J., 1922, i:471. CrossrefGoogle Scholar(6) MOOSBERGER : Schweiz. med. Wchnschr., 1924, liv:325. Google Scholar(7) FINNY : Lancet, 1885, ii:69. Google Scholar(8) OSLER : Modern Medicine, Phila., 1908, iv: 468. Google Scholar(9) BOSTROEM : Deutsch. Arch. f. klin. Med., 1887, xlii:1. Google Scholar(10) ADAMI : Montr. M. J., 1896, xxiv:945. Google Scholar(11) V. SCHNURBEIN : Frankfurt. Zeitschr. f. Path., 1926, xxxiv:532. Google Scholar(12) LOESCHKE : Frankfurt. Zeitschr. f. Path., 1928, xxxvi:56. Google Scholar(13) TODD : Med.-Chir. Trans., Lond., 1844, xxvii:301. CrossrefGoogle Scholar(14) GAGER : Am. Heart J., 1928, iii:489. CrossrefGoogle Scholar(15) BUSSE : Arch. f. path. Anat., 1906, clxxxiii:440. CrossrefGoogle Scholar(16) FREI : Uber das Aneurysma dissecans aortae. Diss. Zűrich, 1921. Google Scholar(17) GOODMAN : J. A. M. A., 1914, lxii: 1242. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LESLIE T. GAGER, M.D.Affiliations: Washington, D. C.*From the Department of Medicine, George Washington University School of Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAortic dissections and dissecting aneurysmsDissecting Aneurysm of the AortaDissecting Aneurysm of the Aorta: Its Clinical, Electrocardiographic and Laboratory FeaturesDissecting aneurysm of aorta with hemorrhagic infarction of the spinal cord and complete paraplegiaDissecting aneurysm of the aortaMedionecrosis aortae idiopathica cystica 1 January 1929Volume 2, Issue 7 Page: 658-664 Keywords Aneurysms Aorta Heart Lesions ePublished: 1 December 2008 Issue Published: 1 January 1929 PDF downloadLoading ...
Hereditary Hyperferritinemia-Cataract Syndrome: Relationship Between Phenotypes and Specific Mutations in the Iron-Responsive Element of Ferritin Light-Chain mRNA
Authors: Mario Cazzola, Gaetano Bergamaschi, Laura Tonon, Eloisa Arbustini, Maurizia Grasso, Elena Vercesi, Giovanni Barosi, Paolo Emilio Bianchi, Gaetano Cairo, Paolo Arosio
Journal: Blood (1997)