tbuckley/cabot-search huggingface dataset:
Heart Association Considers Certifying Hospitals Based on Quality and Results
Authors: Mike Mitka
Journal: JAMA (2011)

trapib comes following disappointing earlier trials investigating CETP inhibition, notably with torcetrapib; a trial assessing clinical outcomes of torcetrapib therapy was terminated in 2006 after the drug was shown to cause excess deaths and cardiovascular events. The question was whether the torcetrapib’s poor showing was a class effect or isolated to that specific drug. “We did not know after torcetrapib failed whether the entire strategy would actually achieve success,” said Steven E. Nissen, MD, chairman of the Cleveland Clinic Foundation’s Department of Cardiovascular Medicine and an investigator of torcetrapib. “I believe the failure of torcetrapib was due to an off-target toxicity, that it increased aldosterone, and that offered the possibility of another CETP inhibitor to show success without that offtarget effect.” Nissen said anacetrapib looks promising, but even after the news from the AHA, the drug’s benefit remains a promise only. “The effect on lipids is what caught everyone’s attention, but I would caution everyone that lipid changes are a surrogate end point, and we have come to be suspicious of surrogate end points; there is not a guarantee of success.” Harlan M. Krumholz, MD, professor of medicine at Yale University School of Medicine in New Haven, Conn, and a skeptic of surrogate end points as providing meaningful results that translate to improved hard outcomes, said Merck is doing the DEFINE trial the right way. “DEFINE is a great prelude to a definitive trial to determine the effect on outcomes, but it is not more than that, so it leaves us ready for the next piece of information,” Krumholz said. “I applaud Merck for proceeding to an outcomes trial.”
Increased Sympathetic Nerve Activity in Renovascular Hypertension
Authors: Mats Johansson, Mikael Elam, Bengt Rundqvist, Graeme Eisenhofer, Hans Herlitz, Gavin Lambert, Peter Friberg
Journal: Circulation (1999)

Increased sympathetic nerve activity may contribute to the progression of renovascular hypertension. Because previous results have been inconclusive, we investigated whether renovascular hypertensives show increased total and regional sympathetic nerve activity.Sixty-five patients underwent renal angiography and measurements of plasma renin activity and angiotensin II in conjunction with estimation of sympathetic nerve activity by means of radiotracer dilution and intraneural recordings of muscle sympathetic nerve activity (MSNA). Age-matched healthy subjects (n=15) were examined for comparison. Total body norepinephrine (NE) spillover, an index of overall sympathetic nerve activity, was increased by 100% and MSNA by 60% in the hypertensive patients compared with healthy subjects (P<0.01 for both). A subgroup of 24 patients with well-defined renovascular hypertension (cured or improved hypertension after renal angioplasty) showed similar increases in total body NE spillover compared with the group at large. Patients with arterial plasma renin activity and angiotensin II levels above median had higher values for total body NE spillover than patients below median (P<0.01).This study unequivocally demonstrates elevated sympathetic nerve activity in patients with renovascular hypertension. The adrenergic overactivity may contribute to the blood pressure elevation and perhaps also to the high cardiovascular mortality in renovascular hypertension.
Pure apocrine carcinomas of the breast express ER-alpha 36, a novel alternatively spliced variant of human estrogen receptor-alpha (ER-alpha 66).
Authors: Z Gatalica, H Deng, LM Lee, Z Wang
Journal: Cancer Research (2009)

Abstract Abstract #4035 Background: Pure apocrine carcinomas (PACs) are defined as tumors composed entirely of epithelium showing apocrine differentiation (large cells with prominent eosinophilic, flocculent cytoplasm with sharply defined borders and large nucleus with prominent macronucleolus). PACs do not express classic estrogen receptor alpha (ER-α66) or progesterone receptor (PR) but consistently over-expresses androgen receptor (AR). We have investigated expression of a novel alternatively spliced variant of ER-α66, named ER-α36, which we recently identified and cloned (Wang ZY et al, PNAS 2006;103: 9063) and demonstrated that it mediates membrane initiated steroid signaling (MISS). MISS is dependent on ER interaction with receptor tyrosine kinases, and we hence investigated co-expression of ER-α36 with EGFR and HER2 in PACs.&amp;#x2028; Methods: 17 patients with breast PAC were studied for expression of ER-α66, PR, AR, HER-2, EGFR and ER-α36 using immunohistochemical methods. ER-α36-specific antibody was custom-made by the Alpha Diagnostic International (San Antonio, TX) against the unique 20 amino acids at the C-terminal of the ER-a36; other antibodies were from commercially available sources. Mammary carcinoma cell line (MDA-MB-231) that lacks expression of ER-α66 but expresses ER-α36 and EGFR, was used as a positive control.&amp;#x2028; Results: All tumors showed characteristic steroid receptor expression profile of apocrine carcinomas (ERα66 and PR negative; AR strongly positive). ERα36 expression was detected in 16/17 cases (94%) in membranous and cytoplasmic distribution. Co-expression of ER-α36 with either one of the tyrosine kinase receptors (HER2 or EGFR) was detected in 16 cases (100% of ER-α36 positive PACs). In an experimental model (MDA-MB-231 cells), 17β-estradiol (E2) strongly induced rapid phosphorylation of the MAPK/ERK1/2, but had only a weak effect in ER-α36 siRNA knock-down MDA-MB-231 cells.&amp;#x2028; Conclusion: Despite the lack of classic full length ER-alpha expression (ER-α66) in PACs, a novel alternatively splice variant (ER-α36) is commonly expressed in this aggressive tumor type. This receptor variant is capable of strong E2 signal transduction and responsible for an increased cell growth. This non-genomic estrogen signaling probably involves membranous interaction between a tyrosine kinase receptor (EGFR or HER2) and ER-α36, resulting in activation of mitogen activated protein kinase pathway. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4035.
Particle Concentrations in Urban Microenvironments
Authors: Jonathan I. Levy, E. Andres Houseman, Louise Ryan, Dejuran Richardson, John D. Spengler
Journal: Environmental Health Perspectives (2000)

Although ambient particulate matter has been associated with a range of health outcomes, the health risks for individuals depend in part on their daily activities.Information about particle mass concentrations and size distributions in indoor and outdoor microenvironments can help identify high-risk individuals and the significant contributors to personal exposure.To address these issues in an urban setting, we measured particle count concentrations in four size ranges and particulate matter ≤ 10 µm (PM 10 ) concentrations outdoors and in seven indoor microenvironments in Boston, Massachusetts.Particle counts and PM 10 concentrations were continuously measured with two light-scattering devices.Because of the autocorrelation between sequential measurements, we used linear mixed effects models with an AR-1 autoregressive correlation structure to evaluate whether differences between microenvironments were statistically significant.In general, larger particles were elevated in the vicinity of significant human activity, and smaller particles were elevated in the vicinity of combustion sources, with indoor PM 10 concentrations significantly higher than the outdoors on buses and trolleys.Statistical models demonstrated significant variability among some indoor microenvironments, with greater variability for smaller particles.These findings imply that personal exposures can depend on activity patterns and that microenvironmental concentration information can improve the accuracy of personal exposure estimation.
New Compound Inhibits Elusive Protein Behind Many Cancers
Authors: Tracy Hampton
Journal: JAMA (2014)

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
Viral Hepatitis in HIV Infection
Authors: Margaret James Koziel, Marion G. Peters
Journal: New England Journal of Medicine (2007)

Liver disease due to chronic HBV or HCV infection is becoming a leading cause of death among persons with HIV infection. Both the risk of hepatocellular carcinoma and the risk of hepatotoxicity due to antiretroviral drugs increase in patients with coinfection. This review presents an approach to the use of newer treatments for both HCV and HBV infections in patients with HIV infection, and it provides an update on optimal management to prevent complications of advanced liver disease.
Measurement and Data Collection in Medical Practice
Authors: Stephen K. Plume
Journal: Annals of Internal Medicine (1998)

Letters1 November 1998Measurement and Data Collection in Medical PracticeStephen K. Plume, MD, Mark E. Splaine, MD, MS, and Eugene C. Nelson, DSc, MPHStephen K. Plume, MDDartmouth-Hitchcock Medical Center; Lebanon, NH 03756Search for more papers by this author, Mark E. Splaine, MD, MSDartmouth-Hitchcock Medical Center; Lebanon, NH 03756Search for more papers by this author, and Eugene C. Nelson, DSc, MPHDartmouth-Hitchcock Medical Center; Lebanon, NH 03756Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-9-199811010-00037 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Drs. Ault and Chander for their interest in our work and their endorsement of our approach. As Dr. Ault points out, current technology makes it possible to include data capture as a routine and helpful part of daily clinical care. As we design the templates for which data we want, it makes sense to us to imagine what our year-end reports should look like. Data captured on the fly, case by case, should be readily aggregated into useful summaries that will help us plan our future programs and budgets.Dr. Chander makes a different kind of ... Author, Article, and Disclosure InformationAffiliations: Dartmouth-Hitchcock Medical Center; Lebanon, NH 03756 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1998Volume 129, Issue 9Page: 754KeywordsForecasting Issue Published: 1 November 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Candidate genes in polycystic ovary syndrome
Authors: Stephen Franks, Neda Gharani, Mark McCarthy
Journal: Human Reproduction Update (2001)

The candidate gene approach has already paid some dividends in trying to understand the complex genetics of polycystic ovary syndrome (PCOS). In terms of steroidogenic abnormalities, CYP11a—encoding P450 side chain cleavage—appears to be a major susceptibility locus. In relation to the well-described metabolic disturbances in PCOS, the insulin gene variable number tandem repeat (VNTR) appears to be a promising candidate, at least in populations studied in the UK. Finally, genes implicated in ovarian follicular development may have a role in the aetiology of PCOS, as demonstrated by recent identification of the follistatin gene as a potential disease locus. It seems unlikely that PCOS can be explained on the basis of a single gene disorder although, in a given family, one gene may have a predominant effect. An oligogenic model seems the most appropriate basis on which to understand the genetic origins of this very common disorder. The candidate gene approach has been useful to date, but it may prove important in the near future to perform an anonymous genome-wide scan to identify hitherto unheralded susceptibility loci.
GW25-e4473 Etiology, location, and spontaneous rupture of aortic pseudoaneurysm: A retrospective study over 10 years
Authors: Huang Yingxiong, Ye Zi, Zheng Zi-Yu, Zhan Hong, Chang Guang-Qi, Cai Rui-Bing, Liu Jiang-Hui, Wang Ke-Ke, Huang Yong
Journal: Journal of the American College of Cardiology (2014)
Abstract P3-10-33: Mammostrat® as an Immunohistochemical Multigene Assay for Prediction of Early Relapse Risk in Postmenopausal Early Breast Cancer: Preliminary Data of the TEAM Pathology Study
Authors: JMS Bartlett, KJ Bloom, NS Goldstein, CJH van de Velde, DT Ross, RS Seitz, RA Beck, A Hasenburg, D Kieback, H Putter, C Markopoulos, L Dirix, T Robson, C Seynaeve, D. Rea
Journal: Cancer Research (2010)

Abstract Background: Postmenopausal early breast cancer patients, treated with endocrine therapy, have approximately 90% five year disease free survival (DFS). However, for patients at higher risk of relapse, additional adjuvant chemotherapy may be indicated. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients on tamoxifen (T) therapy into various risk groups potentially guiding treatment choices. We tested the efficacy of this panel in the TEAM trial (exemestane (E) versus T→E) to determine the relevance in patients treated with an AI. Patients &amp; Methods: Pathology blocks from 4598 TEAM patients were collected and tissue microarrays constructed. The cohort overall was 47% node positive, and 36% also received adjuvant chemotherapy. Samples were stained, using triplicate 0.6mm2 TMA cores, and positivity for p53, HTF9C, CEACAM5, NDRG1, SLC7A5 assessed. Each case was assigned a Mammostrat risk score and analysed for disease free survival (DFS) by marker positivity and risk score. Results: Preliminary results on the UK TEAM cohort (1059 cases) showed 18.9% stained positive for p53 (184/972), 21.3% for NRDG1 (204/956), 26.4% for SLC7A (253/957), 21.9% for HTF9C (220/1004), 18.3% for CEACAM5 (185/1009). Complete data was available for 919 cases including patients treated with chemotherapy, with 447 (49%) designated low risk, 213 (23%) medium and 259 (28%) high risk. In univariate analysis, Mammostrat scores were prognostic (p=0.02), with 5 year DFS (see comment above) results being 86.9±1.7%, 80.1±3.0% and 80.8±2.6% for patients with low, medium and high Mammostrat scores respectively. Analyses on the entire TEAM pathology cohort are ongoing, and further data with sufficient power to evaluate the impact of Mammostrat in multivariate regression analyses will be presented. Conclusion: Preliminary analysis of the impact of the Mammostrat score in both tamoxifen and exemestane treated patients suggests it retains its prognostic value in this context. Further analysis with the power to evaluate the impact of Mammostrat in multivariate regression analyses will be presented. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-33.
Diseases of the Urinary System (Surgical) (Diagnostic and Operative Techniques for the Urinary System)
Authors: E Belt
Journal: Annual Review of Medicine (1955)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Pleural Fluid Complement in Systemic Lupus Erythematosus and Rheumatoid Arthritis
Authors: GENE G. HUNDER
Journal: Annals of Internal Medicine (1972)

Whole hemolytic complement and three components (C1q, C4, and C3) were measured in pleural fluids obtained from 50 patients—23 with malignant disease, 6 with lupus erythematosus, 6 with rheumatoid arthritis, 3 with congestive heart failure, 3 with pulmonary embolism, and 9 in whom the cause of the pleural effusion was not ascertained. The mean values for whole complement and the three components were lowest in lupus erythematosus and rheumatoid arthritis patients. Compared with the malignant disease group, these differences were statistically significant (P < 0.01) for whole complement, C4, and C3. Anticomplementary activity was found in pleural fluids from some patients with lupus erythematosus or rheumatoid arthritis. This suggests that the pleural fluid complement depletion may be secondary to immunologic inactivation and that immune mechanisms may contribute to the development of Pleuritis in lupus erythematosus and rheumatoid arthritis.
Kremers and Urdang's History of Pharmacy
Authors: Lester S. King
Journal: JAMA (1964)

In the history of pharmacy, so intimately connected with the history of medicine, the text of Kremers and Urdang has for many years been the standard work in English. Its last edition, however, was published in 1951. Retaining the main out-line of the original text, Dr. Sonnedecker has given us a revision which is indeed welcome. There are many changes. The page size has been increased and the two-column format utilized, but the total number of pages has been diminished from 622 to 464. Dr. Sonnedecker has closely adhered to the major outlines of the exposition, although one chapter on the developments in Spain has been omitted. The entire text has been rewritten, the changes sometimes taking the form merely of a few transposed phrases or clauses, and other times of substantial new insertions or omissions. The exposition flows smoothly and reads easily. The illustrations, increased more than threefold, are
Diagnosis of asthma and permitted use of inhaled <i>β</i><sub>2</sub>‐agonists in athletes
Authors: S. Bonini, V. Brusasco, K.‐H. Carlsen, L. Delgado, S. D. Giacco, T. Haahtela, G. Rasi, P. B. van Cauwenberge
Journal: Allergy (2003)

The prevalence of asthma and bronchial hyperreactivity has been reported to be higher in athletes than in the general population. This has also been related to reported asthma in order to obtain permitted use of β 2 ‐agonists, whose assumption in athletes is ruled by anti‐doping regulations. The paper addresses the issue whether the recently established and evaluated rules of the International Olympic Committee on tests and procedures for diagnosis of asthma in athletes and permitted use of β 2 ‐agonists are consistent with an adequate diagnosis and management of asthma according to international guidelines.
High Bioavailability of Bisphenol A from Sublingual Exposure
Authors: Véronique Gayrard, Marlène Z. Lacroix, Séverine H. Collet, Catherine Viguié, Alain Bousquet-Melou, Pierre-Louis Toutain, Nicole Picard-Hagen
Journal: Environmental Health Perspectives (2013)

Bisphenol A (BPA) risk assessment is currently hindered by the rejection of reported higher-than-expected plasma BPA concentrations in humans after oral ingestion. These are deemed incompatible with the almost complete hepatic first-pass metabolism of BPA into its inactive glucurono-conjugated form, BPA glucuronide (BPAG).Using dogs as a valid model, we compared plasma concentrations of BPA over a 24-hr period after intravenous, orogastric, and sublingual administration in order to establish the absolute bioavailability of BPA administered sublingually and to compare it with oral bioavailability.Six dogs were sublingually administered BPA at 0.05 mg/kg and 5 mg/kg. We compared the time course of plasma BPA concentrations with that obtained in the same dogs after intravenous administration of the same BPA doses and after a 20-mg/kg BPA dose administrated by orogastric gavage.The data indicated that the systemic bioavailability of BPA deposited sublingually was high (70-90%) and that BPA transmucosal absorption from the oral cavity led to much higher BPA internal exposure than obtained for BPA absorption from the gastrointestinal tract. The concentration ratio of BPAG to BPA in plasma was approximately 100-fold lower following sublingual administration than after orogastric dosing, distinguishing the two pathways of absorption.Our findings demonstrate that BPA can be efficiently and very rapidly absorbed through the oral mucosa after sublingual exposure. This efficient systemic entry route of BPA may lead to far higher BPA internal exposures than known for BPA absorption from the gastrointestinal tract.
Ciguatera Fish Poisoning
Authors: Denise M. Goodman, Jennifer Rogers, Edward H. Livingston
Journal: JAMA (2013)

Ciguatera Fish PoisoningGrouper Barracuda Amberjack Snapper 20 µm Source of ciguatera toxins in tropical and subtropical fish Ciguatera toxins are produced by microalgae called Gambierdiscus toxicus that can grow on seaweed, dead coral, and other surfaces.Small fish eat the toxic microalgae while grazing.
Streptokinase-induced platelet aggregation. Prevalence and mechanism.
Authors: D E Vaughan, E Van Houtte, P J Declerck, D Collen
Journal: Circulation (1991)

BACKGROUND Streptokinase (SK) is a bacteria-derived protein and one of the plasminogen activators that is currently available for therapeutic use. Exposure to SK induces synthesis of specific antibodies that may initiate platelet aggregation and paradoxical clot propagation during treatment. METHODS AND RESULTS Using platelet-rich plasma (PRP), we found that SK (5,000 units/ml) but not urokinase (2,500 units/ml) or recombinant tissue-type plasminogen activator (2,500 units/ml) caused platelet aggregation in PRP from 14 of 100 normal volunteers. In 13 consecutive patients treated with SK for acute myocardial infarction, SK-mediated platelet aggregation was induced in five patients within 1 week after treatment. SK-mediated platelet aggregation was associated with significantly increased titers of both anti-SK antibodies and SK-neutralizing activity in plasma; it was partially inhibited by aspirin (1 mM) and by aprotinin (500 kallikrein inhibitor units/ml) and completely inhibited by tranexamic acid (1 mM) and by prostaglandin E1 (9 microM). Addition of SK (1,000 or 5,000 units/ml) induce a statistically significant dose-dependent thromboxane B2 release in mixtures of PRP with plasma from subjects with SK-induced aggregation but not in samples of PRP mixed with plasma from nonresponders; addition of recombinant tissue-type plasminogen activator (1 or 50 micrograms/ml) did not induce thromboxane B2 release. Mixing experiments with PRP and immunoglobulin G from reactive and nonreactive donors revealed that SK-induced aggregation requires the presence of anti-SK antibodies. When 125I-SK (50 nM) was used, platelets preincubated with plasminogen (0.5 microM) bound 9,500 +/- 600 (mean +/- SEM, n = 6) molecules SK/platelet, which increased to 25,000 +/- 3,100 molecules/platelet after thrombin stimulation. Tranexamic acid (1 mM) blocked specific binding of SK to resting platelets. CONCLUSIONS These data demonstrate that SK-induced platelet aggregation is initiated by the binding of anti-SK antibodies to the SK-plasminogen complex located on the platelet surface. SK-induced platelet activation may limit the therapeutic effectiveness of the drug, and in view of the high prevalence of aggregation in a normal population, prospective evaluation of the effects of platelet aggregation during treatment with SK is warranted.