tbuckley/cabot-search huggingface dataset:
To Have Been or Not to Have Been
Authors: Lester H. Hoyt
Journal: JAMA (1965)

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 Journals 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 2024 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 4498: HS-104, a novel potent phosphatidylinositol 3-kinase inhibitor, with anticancer activity in human hepatocellular carcinoma
Authors: Soon-Sun Hong, Hong-Mei Zheng, Kyung Hee Jung, Hyunseung Lee, Sang-Won Hong, Guang-Yong Li, Byung-Hee Park, Mi-Kwon Son
Journal: Cancer Research (2011)

Abstract Phosphatidylinositol 3-kinase (PI3K) has been implicated in cell growth, proliferation, and survival in a variety of diseases including cancer. It is activated by mutational activation of PI3Kα, loss of function of PTEN or activation of receptor tyrosine kinases. A number of PI3K inhibitors have recently been developed for use in cancer therapy. However, there has been no report performed in human hepatocellular carcinoma (HCC), even if the mutation of PI3Ka in HCC have been reported as 6.0∼35.6%. In this study we investigated the effect of HS-104, a novel phosphatidylinositol 3-kinase inhibitor on the proliferation, apoptosis, angiogenesis of HCC cells as well as in vivo mouse xenograft model bearing Huh-7 HCC cells. HS-104 inhibited PI3Ka activity more than LY294002 (a traditional PI3K inhibitor), and it suppressed the phosphorylation of Akt and mTOR in downstream of PI3K in a dose dependent manner. The growth of HCC cells (Huh-7, HepG2, Hep3B) was inhibited by HS-104 treatment in a dose-dependent manner as sorafenib did. Interestingly HS-104 didn't affect the normal liver cell line (HL-7702), while sorafenib showed cytotoxicity at high concentrations. Also, its induction of apoptosis was found by the increase in the proportion of sub-G1 apoptotic cells of 20% at a dose of 10 uM, and the increase in the expressions of cleaved PARP and caspase-3 as well as the decrease in that of bcl-2 in Huh-7 cells. Its induction of apoptosis was confirmed by DNA fragmentation as well as DAPI and TUNEL staining. In addition, we found that HS-104 decreased the expression of hypoxia-inducible factor (HIF-1α), vascular endothelial growth factor (VEGF), and the tube formation and migration of human umbilical vein endothelial cells (HUVECs) in a dose dependent manner, which were confirmed by Matrigel plug assay performed in BALB/c nude mouse. In addition, HS-104 administration (10 mg/kg) for two weeks significantly suppressed the growth of liver cancer in mouse xenograft model using Huh-7 cells, where its induction of apoptosis and anti-angiogenesis was confirmed by immunohistochemistry assay for tumor tissues. Taken together, these results suggest that HS-104 could be used as a drug for the treatment of human hepatoma cells by the mechanism of apoptosis and anti-angiogenesis. 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 4498. doi:10.1158/1538-7445.AM2011-4498
STATIN REDUCES LATE TLR (BEYOND 1YEAR) &amp;ldquo;LATE CATCH UP PHENOMENON&amp;rdquo; AS WELL AS EARLY TLR (WITHIN 1YEAR) AFTER SIROLIMUS-ELUTING STENT IMPLANTATION: FROM J-CYPHER REGISTRY
Authors: Yoshihiro Katoh, Masahiro Natsuaki, Yoshihisa Nakagawa, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2012)
Acute brachial artery thrombosis as the initial manifestation of human immunodeficiency virus infection
Authors: Misha Witz, Jonathan Lehmann, Ze'ev Korzets
Journal: American Journal of Hematology (2000)

Thrombosis of upper extremity arteries is most commonly due to atherosclerosis of the proximal subclavian artery, trauma, or catheter-related injury. In the absence of an identifiable cause, a search for a hypercoagulable state is indicated. Hematologic manifestations of human immunodeficiency virus (HIV) infection and AIDS are frequent occurrences (Coyle TE. Med Clin N Am 1997;81:449–476). The most important of these are cytopenias (anemia, neutropenia, and thrombocytopenia). The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. In addition, various coagulation abnormalities have been reported in HIV-infected patients. Apart from thrombocytopenia, these have included a prolonged APTT due to the presence of lupus anticoagulant, an increased prevalence of protein S and heparin cofactor II deficiency, and hypoalbuminemia-related fibrin polymerization defects (Toulon P. Ann Bio Clin (Paris) 1998;56:153–160). HIV infection has also been associated with endothelial dysfunction. Although for the most part asymptomatic, elevated d-dimer levels have been found in HIV-infected patients, suggesting the existence of a prethrombotic state. In fact, clinical thrombosis eventuates in 2% of these patients (Toulon, 1988). Documented thromboses have involved both veins and arteries. We hereby present a patient who developed an acute thrombosis of his brachial artery as the initial manifestation of HIV infection. Am. J. Hematol. 64:137–139, 2000. © 2000 Wiley-Liss, Inc.
Corticosteroids in acute severe asthma: effectiveness of low doses.
Authors: S D Bowler, C A Mitchell, J G Armstrong
Journal: Thorax (1992)

Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known.The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days.The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose.Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.
Adalimumab for the treatment of psoriasis in real life: a retrospective cohort of 119 patients at a single Spanish centre
Authors: A. López-Ferrer, E. Vilarrasa, I.J. Gich, L. Puig
Journal: British Journal of Dermatology (2013)

Patients with moderate-to-severe psoriasis treated with adalimumab in daily clinical practice are different from those in clinical trials, and outcomes may differ in different geographical settings.To analyse the efficacy, retention of treatment and adverse events in a cohort of such patients at a referral centre in Barcelona, Spain.Data from a cohort of 119 consecutive patients treated between January 2008 and March 2013 were retrospectively collected. Drug survival was analysed by the Kaplan-Meier method with log-rank test and Cox regression.The mean duration of treatment was 25 months (median 22, range 2-60). The 75% improvement in Psoriasis Area and Severity Index (PASI 75) response rates at 16 weeks, 6 months and 1 year of treatment were 64%, 58% and 53%, respectively (intention-to-treat analysis). The corresponding PASI 90 values were 49%, 52% and 50%. Biologic-naive patients (41%) had significantly higher PASI 75 and PASI 90 response rates at 6 months and 1 year. On multivariate analysis, only PASI 90 response at 6 months was significantly associated with treatment retention (P = 0.0009), with a hazard ratio of 7.3 (95% confidence interval 2.3-23.6). Forty-eight adverse events (AEs) occurred in 29 patients, and were serious in eight (0.032 events per patient-year). Paradoxical flares of psoriasis or arthritis were seen in five patients. Infections accounted for seven serious AEs, and were the reason for discontinuation in two patients.PASI 90 response at 6 months was the only independent variable predicting drug survival on multivariate analysis. Infections, including de novo infection by Mycobacterium tuberculosis, accounted for seven serious AEs.
Lansley promises to review health bill after Liberal Democrats oppose reforms
Authors: N. Hawkes
Journal: BMJ (2011)

Andrew Lansley, the secretary of state for health, has signalled a willingness to make changes to the Health and Social Care Bill to conciliate rebellious Liberal Democrats.

At their weekend conference Liberal Democrat members rejected their party leadership’s support for Mr Lansley’s reforms of the health service in England. To persuade sceptical Liberal Democrats in parliament to approve the bill, Mr Lansley will now need to make some concessions. The question is whether these will prove substantive or merely cosmetic.

The amendment passed by the party conference makes three major points. It rejects what it sees as a “damaging and unjustified” market based approach in the bill, warns of the risk of private companies “cherry picking” profitable services, and urges that commissioning should be made publicly accountable by requiring “about …
Isolation of a complementary DNA clone for the human complement protein C2 and its use in the identification of a restriction fragment length polymorphism.
Authors: D E Woods, M D Edge, H R Colten
Journal: Journal of Clinical Investigation (1984)

Complementary DNA (cDNA) clones corresponding to the major histocompatibility (MHC) class III antigen, complement protein C2, have been isolated from human liver cDNA libraries with the use of a complex mixture of synthetic oligonucleotides (17 mer) that contains 576 different oligonucleotide sequences. The C2 cDNA were used to identify a DNA restriction enzyme fragment length polymorphism that provides a genetic marker within the MHC that was not detectable at the protein level. An extensive search for genomic polymorphisms using a cDNA clone for another MHC class III gene, factor B, failed to reveal any DNA variants. The genomic variants detected with the C2 cDNA probe provide an additional genetic marker for analysis of MHC-linked diseases.
Cohesion of horny cells during comedo formation.
Authors: P. C. WOO-SAM
Journal: British Journal of Dermatology (1977)

Cohesion between horny cells was studied in experimentally induced comedones, from the rabbit's external ear canal. It occurred in two different ways: initially, by the persistence of desmosones and desmonosmal bodies (fusiform electron dense bodies), which loosely held the horny cells together; later, and to a lesser extent, by tight junctions, which tightly bound the horny cells together. A gradual decrease in the numbers of membrane coating granules was observed.
A SIMPLE METHOD for DEMONSTRATING the PRODUCTION of GAS by BACTERIA
Authors: H. E. Durham
Journal: BMJ (1898)

On February 7th lafge sloughs appeared on both buttocks in spite of the use of an air bed, etc.; later diarrhoea set in, and the patient succumbed on February 12tll, just a month after admission.The treatment main- tained throughout was in the direction of local disinfection and support- ingthe patient's strength, amputation being out of the question.
The Renin-Angiotensin System
Authors: Ruth C. Campbell
Journal: Journal of the American Society of Nephrology (2004)

The classical role of the renin-angiotensin system (RAS) has been to serve as a vasoconstrictor and to facilitate renal sodium absorption, serving to maintain BP. A puzzling aspect of the RAS, however, has been the existence of low-renin hypertensive states, defined as a low plasma renin activity (
Neutropenias following allogeneic bone marrow transplantation: Response to therapy with high-dose intravenous immunoglobulin
Authors: Issa F. Khouri, Cindy Ippoliti, James Gajewski, Donna Przepiorka, Richard E. Champlin
Journal: American Journal of Hematology (1996)

Cytopenias following bone marrow transplantation may be severe and life-threatening. These have been described post-allogeneic Klumpp, 1991: Bone Marrow Transplant 8:159-171. or post-autologous bone marrow transplants Khouri et al., 1994: J Clin Oncol 12:748-758. as well as with peripheral blood stem cell transplantation Klumpp et al., 1992: Am J Hematol 41:215-217. It can be immune mediated, associated on occasions with graft-versus-host disease (GVHD) Anasetti et al., 1989: Blood 4:1054-1058; however, in most cases, the underlying mechanism is uncertain. The treatment of post-transplant cytopenias is not well established, and they are often refractory to immunosuppressive therapy with steroids. Herein we describe two cases of neutropenia after allogeneic bone marrow transplantation that improved after therapy with high-dose intravenous immunoglobulin.
Immunology for Surgeons
Authors: Robert E. McCabe
Journal: JAMA (1977)

Surgeons have long looked on the mystical concepts of immunology as a form of foreign tissue that interferes with their role in curing disease. The dawn of "the golden age of spare parts surgery" has, however, forced on all surgeons reexamination of this rapidly expanding field of scientific achievement. The role of immunology in the etiology and treatment of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and systemic lupus, as well the development and control of malignant disease, is now broadly accepted by all surgeons. <i>Immunology for Surgeons</i>, edited by J. E. Castro, adds one more volume to a growing list of texts dealing with surgical immunology and must therefore compete with the surgeons' immunologic bible written by Belanti. The chapters include standard basic scientific material related to antigen-antibody responses, the role of complement, mechanisms of immunologic disease, immunosuppression, enhancement, and the production of immunologic tolerance. Dr Castro himself
Paradoxical Suppression of Chorea by Apomorphine
Authors: Eduardo S. Tolosa
Journal: JAMA (1974)

To the Editor.—  Choreiform movements in a variety of clinical syndromes appear to be physiologically related to abnormal functions of the corpus striatum. It has been recently proposed that increased responsiveness of striatal dopamine (DA) receptors to DA underlies these abnormal movements. 1 To further delineate the role of DA in the production of chorea we administered apomorphine (subcutaneously) in doses of 1 to 2 mg, and placebo in similar doses, to five patients: two with tardive dyskinesias, two with spontaneous orofacial dyskinesias, and one patient with congenital choreoathetosis. In four of the five patients, a moderate to marked, though transie.it (45 to 80 minutes), reduction of choreiform movements was observed after apomorphine administration, while little change in abnormal movements was noted after placebo injections. One patient with spontaneous dyskinesias did not show any improvement in chorea. Side effects such as nausea and vomiting, hypotension, or sedation occurred in all
Desloratadine reduces nasal congestion and other signs and symptoms of allergic rhinitis (AR) induced by house dust mite (HDM) allergen exposure in the Vienna Challenge Chamber
Authors: U.P. Stuebner, F. Horak, R. Zieglmeyer, A. Kawina, W. Engelbrecht, M. Moser, A.G. Harris
Journal: Journal of Allergy and Clinical Immunology (2003)
Predictors for failure of Pneumocystis carinii pneumonia prophylaxis. Multicenter AIDS Cohort Study
Authors: A. J. Saah
Journal: JAMA (1995)

To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis.Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200 x 10(9)/L (200/microL).Occurrence or recurrence of PCP.A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine--367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P = .19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050 x 10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P < .001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P = .01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P = .03).These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required.
Harms of target driven health care
Authors: N. Rawlinson
Journal: BMJ (2008)

I went to listen to a senior member from the Department of Health explain the new “dogma” of target driven health care to our hospital’s consultant group. This was in 2005, as we were coming to terms with the fact of targets and with their use to drive healthcare performance. After her slick presentation I asked how the government was going to measure the harm that these targets would do to patient care. I remember being amazed at the skill with which that question was not answered.

From 2003 to 2006 I was associate clinical director of the emergency department at the Bristol Royal Infirmary. I soon realised that targets were here to stay, and led the unit to accept this and work with them. The phrase “I treat patients, not targets” was consigned to the past. We had to engage with the targets that had been set, and use them to attract the resources we needed to treat patients faster. We had a philosophy in the department that was forward thinking, aiming to find solutions rather than identify problems. The trust recognised this and supported us, and we met the 98% …
Comparison of the relative airways and systemic potencies of inhaled fenoterol and salbutamol in asthmatic patients.
Authors: B J Lipworth, D M Newnham, R A Clark, D P Dhillon, J H Winter, D G McDevitt
Journal: Thorax (1995)

BACKGROUND--There is controversy as to the relative safety of fenoterol and salbutamol. No differences have been found in the relative cardiac beta 1/beta 2 receptor activity of inhaled fenoterol and salbutamol in normal subjects. These initial findings have been extended by comparing the respective potencies of equivalent doses by weight of fenoterol and salbutamol in asthmatic subjects, in terms of airways and systemic responses. METHODS--Eighteen asthmatic patients of mean (SD) age 40 (14) years and a forced expiratory volume in one second (FEV1)% predicted of 56 (14)% (1.97 (0.66)1) were randomised to inhale fenoterol (100 micrograms/puff or 200 micrograms/puff), salbutamol, or placebo (100 micrograms/puff or 200 micrograms/puff) on three separate days. Dose-response curves were constructed using cumulative doses of 100 micrograms, 200 micrograms, 400 micrograms, 1000 micrograms, 2000 micrograms, and 4000 micrograms, and airways and systemic responses were measured 20 minutes after each dose with 40 minute increments. Dose ratios for the relative potency of fenoterol versus salbutamol were calculated from the dose-response curves using regression analysis of parallel slopes. RESULTS--There was no difference in bronchodilator potency between fenoterol and salbutamol (as median dose ratio): FEV1 1.1 (95% CI 0.4 to 4.6). In contrast, dose ratios for systemic responses showed that fenoterol was more potent than salbutamol: serum potassium 3.7 (95% CI 2.0 to 6.0), tremor 5.7 (95% CI 1.4 to 10.2), heart rate 1.6 (95% CI 1.0 to 2.3). At a conventional dose of 200 micrograms the only difference in response between the two drugs was observed for tremor (as mean difference): 0.23 log units (95% CI 0.06 to 0.41 log units). CONCLUSIONS--There was no difference in the bronchodilator potency between fenoterol and salbutamol on a microgram equivalent basis. In contrast, systemic potency was greater with fenoterol, although this difference was not clinically relevant at conventional dosages up to 200 micrograms.
A Global Positioning System for the Colon?
Authors: S. Friedland, J. Van Dam
Journal: Endoscopy (2002)

Like the ubiquitous global positioning system (GPS), which uses orbiting satellites to determine the precise location of a receiver anywhere on Earth, the magnetic endoscope imager (MEI) is a technically advanced system capable of pinpointing the precise three-dimensional location of a colonoscope within the body. While GPS has revolutionized air, land, and sea travel, it remains to be seen whether MEI will have an equally profound impact on colonoscopic navigation.