tbuckley/cabot-search huggingface dataset:
Restriction of Non-Prescription Drugs
Authors: Walter Singer
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In your commentary on analgesic abuse and the kidney (<i>JAMA</i><b>190</b>:238 [Oct 19] 1964) you point to the incomplete and misleading nature of the warning now required by Food and Drug Administration regulation to appear on all packages of phenacetin-containing drugs for over-the-counter use. You also indicate the dangers of aspirin abuse and our lack of knowledge about acetaminophen hazard. You question the wisdom of any label warning directed against<i>abuse</i>, with special reference to ineffectiveness for people whose psychological makeup leads them to excesses. I agree with you that it is not possible by label warning alone to protect the public against hazards of self-medication with these or many other drugs. Unfortunately, such drugs are widely available. Recently the American Pharmaceutical Association has asked for establishment of a federal classification of non-prescription drugs which can be obtained only from pharmacists. Phenacetin-containing drugs would undoubtedly be
Surgical Management of Abortion
Authors: Jacob F. Palomaki, A. Brian Little
Journal: New England Journal of Medicine (1972)

IN Europe and Asia, legal abortion has been performed in relation to demographic and socioeconomic considerations, inadequate contraceptive programs, the desire to protect women from illegal abortions and the belief that women have a right to determine the desirability of a particular pregnancy.1 In the United States, abortion has legally been restricted to cases in which the mother's life or physical health was threatened. However, with the enactment of liberalized laws in 17 states since 1967, abortion has become more readily available to the average American woman.2 Patient PreparationAbortion is primarily a surgical procedure. Evaluation and management of the . . .
Prednisone Treatment for Idiopathic Facial Paralysis (Bell's Palsy)
Authors: Kedar K. Adour, John Wingerd, Douglas N. Bell, John J. Manning, J. Pearce Hurley
Journal: New England Journal of Medicine (1972)

The effects of prednisone administered orally to 194 patients with idiopathic facial paralysis (Bell's palsy) were compared with the outcome in 110 untreated patients. The treated group experienced fuller recovery and less severe complications. Of the patients with clinically complete paralysis, 24 per cent of the untreated group and none of the treated group had complete denervation. Differences in mean Recovery Profile and Recovery Index were also significant. Complications of prednisone treatment occurred in fewer than 4 per cent of patients. Facial-nerve edema is found in the acute stage of idiopathic facial paralysis, and may be the first step in the events leading to the neuropathy. Treatment with prednisone may reduce this edema along the entire facial nerve, and may be preferable to surgical decompression.
918 ACUTE LIVER FAILURE IN GERMANY 2008-2009: A RETROSPECTIVE ANALYSIS BY THE ACUTE LIVER FAILURE STUDY GROUP GERMANY
Authors: J. Hadem, F. Tacke, T. Bruns, J. Langgartner, P. Strnad, G. Denk, P. Fikatas, M.P. Manns, W.P. Hofmann, G. Gerken, F. Grünhage, A. Umgelter, C. Trautwein, A. Canbay
Journal: Journal of Hepatology (2011)
Interleukin-10 Treatment Attenuates Pressure Overload–Induced Hypertrophic Remodeling and Improves Heart Function via Signal Transducers and Activators of Transcription 3–Dependent Inhibition of Nuclear Factor-κB
Authors: Suresh Kumar Verma, Prasanna Krishnamurthy, David Barefield, Neha Singh, Rajesh Gupta, Erin Lambers, Melissa Thal, Alexander Mackie, Eneda Hoxha, Veronica Ramirez, Gangjian Qin, Sakthivel Sadayappan, Asish K. Ghosh, Raj Kishore
Journal: Circulation (2012)

Background— Inflammation plays a critical role in adverse cardiac remodeling and heart failure. Therefore, approaches geared toward inhibiting inflammation may provide therapeutic benefits. We tested the hypotheses that genetic deletion of interleukin-10 (IL-10), a potent antiinflammatory cytokine, exacerbates pressure overload–induced adverse cardiac remodeling and hypertrophy and that IL-10 therapy inhibits this pathology. Methods and Results— Cardiac hypertrophy was induced in wild-type and IL-10 knockout mice by isoproterenol (ISO) infusion. ISO-induced left ventricular dysfunction and hypertrophic remodeling, including fibrosis and fetal gene expression, were further exaggerated in knockout mice compared with wild-type mice. Systemic recombinant mouse IL-10 administration markedly improved left ventricular function and not only inhibited but also reversed ISO-induced cardiac remodeling. Intriguingly, a very similar cardioprotective response of IL-10 was found in transverse aortic constriction–induced hypertrophy and heart failure models. In neonatal rat ventricular myocytes and H9c2 myoblasts, ISO activated nuclear factor-κB and inhibited signal transducers and activators of transcription 3 (STAT3) phosphorylation. Interestingly, IL-10 suppressed ISO-induced nuclear factor-κB activation and attenuated STAT3 inhibition. Moreover, pharmacological and genetic inhibition of STAT3 reversed the protective effects of IL-10, whereas ectopic expression of constitutively active STAT3 mimicked the IL-10 responses on the ISO effects, confirming that the IL-10–mediated inhibition of nuclear factor-κB is STAT3 dependent. Conclusion— Taken together, our results suggest IL-10 treatment as a potential therapeutic approach to limit the progression of pressure overload–induced adverse cardiac remodeling.
Genome sequencing and analysis of admixed genomes of African and Mexican ancestry: implications for personal ancestry reconstruction and multi-ethnic medical genomics
Authors: Francisco M De La Vega, Katarzyna Bryc, Jeremiah D Degehnardt, Shaila Musharoff, Jeffrey M Kidd, Vrunda Seth, Sarah Stanley, Abra Brisbin, Alon Keinan, Andrew Clark, Carlos D Bustamante
Journal: Genome biology (2010)

Background Understanding the contribution of rare and common genetic variants to disease susceptibility will probably require multiand transethnic sequencing studies that compare the genomes of many individuals with and without a particular disease. Accounting for the role of population stratification at fine scales, both in terms of genomic and geographic location, will be important because rare alleles are likely to show more population stratification. Here, we present results from sequencing, assembly and genomic analysis of two genomes from the Phase 3 HapMap. The donor individuals are of Mexican and African ancestry and represent the first ‘admixed’ genomes to be sequenced to high coverage.
HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation
Authors: Effie W. Petersdorf, Theodore A. Gooley, Mari Malkki, Andrea P. Bacigalupo, Anne Cesbron, Ernette Du Toit, Gerhard Ehninger, Torstein Egeland, Gottfried F. Fischer, Thibaut Gervais, Michael D. Haagenson, Mary M. Horowitz, Katharine Hsu, Pavel Jindra, Alejandro Madrigal, Machteld Oudshoorn, Olle Ringdén, Marlis L. Schroeder, Stephen R. Spellman, Jean-Marie Tiercy, Andrea Velardi, Campbell S. Witt, Colm O’Huigin, Richard Apps, Mary Carrington
Journal: Blood (2014)
Control of Asthma by Aerosols
Authors: Michael T. Newhouse, Myrna B. Dolovich
Journal: New England Journal of Medicine (1986)

PHYSICIANS have been intrigued with the idea of inhalation therapy for more than a century, since patients were advised to smoke cigarettes containing anticholinergic botanicals such as Datura stramonium to obtain relief from asthma attacks.1 The use of aerosols to treat asthma allows an almost ideal therapeutic ratio to be achieved, since minute doses of inhaled medication provide optimal maintenance therapy with minimal side effects.2 3 4 5 6 In severe acute asthma, sympathomimetic bronchodilator aerosols are superior to systemic therapy with the same agents.7 , 8 In chronic asthma, adrenoceptor-agonist aerosols provide greater and more rapid bronchodilatation and are also more effective in preventing airway . . .
Immediate coronary angioplasty for acute myocardial infarction.
Authors: S D Pringle, N A Boon
Journal: BMJ (1993)

Immediate coronary angioplasty for acute myocardial infarction Safe and effective but not available in most centres Almost all myocardial infarctions are caused by a coronary thrombosis secondary to a ruptured atheromatous plaque'2 and evolve over six to 12 hours.Hence thrombolytic treat- ment, when given early enough, can reopen the affected artery, save myocardium, and reduce mortality.After several large randomised studies, oral aspirin and intravenous streptokinase have become the standard treat- ment for acute myocardial infarction in Britain, 6 although there may be problems.There is a small but significant risk of stroke and other bleeding complications.Furthermore, in at least a quarter of patients reperfusion does not occur; and even if it does there may be a residual coronary artery stenosis that will require definitive treatment later.Although "rescue" percutaneous transluminal coronary angioplasty may benefit selected patients,7 there seems no place for routine angioplasty after thrombolysis.89Three recent publications, however, have shown that percutaneous transluminal coronary angioplasty may be of value as an alternative, rather than an adjunct, to thrombolysis."0-'2In these studies a total of 645 patients with acute myocardial infarction received aspirin and heparin and were then randomised to receive either thrombolytic drugs or angiography with a view to immediate angioplasty without thrombolysis.After cardiac catheterisation angioplasty was considered inappropriate in 27 of the 312 patients allocated to this form of treatment and nearly half of these patients were then referred for emergency coronary artery bypass grafting for critical three vessel or left main stem disease.Percutaneous transluminal coronary angioplasty was carried out in all of the remaining patients, the first balloon inflation occurring an
Rearrangements and Amplification of <i>IER3</i> (<i>IEX-1</i>) Represent a Novel and Recurrent Molecular Abnormality in Myelodysplastic Syndromes
Authors: David P. Steensma, Jessemy D. Neiger, Julie C. Porcher, J. Jonathan Keats, P. Leif Bergsagel, Thomas R. Dennis, Ryan A. Knudson, Robert B. Jenkins, Rafael Santana-Davila, Rajiv Kumar, Rhett P. Ketterling
Journal: Cancer Research (2009)

IER3 (formerly IEX-1) encodes a 27-kDa glycoprotein that regulates death receptor-induced apoptosis, interacts with NF-kappaB pathways, and increases expression rapidly in response to cellular stresses such as irradiation. Animal models, gene expression microarray experiments, and functional studies in cell lines have suggested a potential role for IER3 in oncogenesis, but, to date, no abnormalities of IER3 at the DNA level have been reported in patients with neoplasia. Here, we describe breakpoint cloning of a t(6;9)(p21;q34) translocation from a patient with a myelodysplastic syndrome (MDS), facilitated by conversion technology and array-based comparative genomic hybridization, which revealed a rearrangement translocating the IER3 coding region away from critical flanking/regulatory elements and to a transcript-poor chromosomal region, markedly decreasing expression. Using split-signal and locus-specific fluorescence in situ hybridization (FISH) probes, we analyzed 204 patients with diverse hematological malignancies accompanied by clonal chromosome 6p21 abnormalities, and found 8 additional patients with MDS with IER3 rearrangements (translocations or amplification). Although FISH studies on 157 additional samples from patients with MDS and a normal-karyotype were unrevealing, and sequencing the IER3 coding and proximal promoter regions of 74 MDS patients disclosed no point mutations, reverse transcription-PCR results suggested that dysregulated expression of IER3 is common in MDS (61% >4-fold increase or decrease in expression with decreased expression primarily in early MDS and increased expression primarily in later MDS progressing toward leukemia), consistent with findings in previous microarray experiments. These data support involvement of IER3 in the pathobiology of MDS.
Specific Inhibition of HBV Replication In Vitro and In Vivo With Expressed Long Hairpin RNA
Authors: Marc S Weinberg, Abdullah Ely, Samantha Barichievy, Carol Crowther, Steven Mufamadi, Sergio Carmona, Patrick Arbuthnot
Journal: Molecular Therapy (2007)

Activating RNA interference to achieve specific gene silencing has shown promise for the development of RNA-based treatment of chronic hepatitis B virus (HBV) infection. To further this approach, we assessed the efficacy of expressed long hairpin RNAs (lhRNAs) that target the conserved HBx open reading frame of HBV. As substrates for Dicer, lhRNAs have the potential to generate multiple short interfering RNAs (siRNAs) to enable simultaneous targeting of different sites. Two U6 Pol III vectors were constructed that encode anti-HBV lhRNAs with a 62 base pair stem sequence containing multiple G:U pairings. Assessment in transfected cultured cells and also in vivo using the murine hydrodynamic injection model showed that one of the lhRNA vectors (lhRNA 1) diminished markers of virus replication by 70–90% without evidence of interferon response induction. Greatest silencing efficacy was observed for targets that are complementary to sequences located at the base of the hairpin stem and this correlated with a higher concentration of siRNAs derived from this region of the lhRNA. Although lhRNA 1 has the advantage of targeting a greater viral sequence, incomplete cellular processing may result in unequal silencing across the span of the viral target RNA. Activating RNA interference to achieve specific gene silencing has shown promise for the development of RNA-based treatment of chronic hepatitis B virus (HBV) infection. To further this approach, we assessed the efficacy of expressed long hairpin RNAs (lhRNAs) that target the conserved HBx open reading frame of HBV. As substrates for Dicer, lhRNAs have the potential to generate multiple short interfering RNAs (siRNAs) to enable simultaneous targeting of different sites. Two U6 Pol III vectors were constructed that encode anti-HBV lhRNAs with a 62 base pair stem sequence containing multiple G:U pairings. Assessment in transfected cultured cells and also in vivo using the murine hydrodynamic injection model showed that one of the lhRNA vectors (lhRNA 1) diminished markers of virus replication by 70–90% without evidence of interferon response induction. Greatest silencing efficacy was observed for targets that are complementary to sequences located at the base of the hairpin stem and this correlated with a higher concentration of siRNAs derived from this region of the lhRNA. Although lhRNA 1 has the advantage of targeting a greater viral sequence, incomplete cellular processing may result in unequal silencing across the span of the viral target RNA.
Angiogenesis and Cancer
Authors: Carolyn J. Hildreth
Journal: JAMA (2009)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice
Authors: Rupal Ramakrishnan, Deepak Assudani, Srinivas Nagaraj, Terri Hunter, Hyun-Il Cho, Scott Antonia, Soner Altiok, Esteban Celis, Dmitry I. Gabrilovich
Journal: Journal of Clinical Investigation (2010)

Cancer immunotherapy faces a serious challenge because of low clinical efficacy. Recently, a number of clinical studies have reported the serendipitous finding of high rates of objective clinical response when cancer vaccines are combined with chemotherapy in patients with different types of cancers. However, the mechanism of this phenomenon remains unclear. Here, we tested in mice several cancer vaccines and an adoptive T cell transfer approach to cancer immunotherapy in combination with several widely used chemotherapeutic drugs. We found that chemotherapy made tumor cells more susceptible to the cytotoxic effect of CTLs through a dramatic perforin-independent increase in permeability to GrzB released by the CTLs. This effect was mediated via upregulation of mannose-6-phosphate receptors on the surface of tumor cells and was observed in mouse and human cells. When combined with chemotherapy, CTLs raised against specific antigens were able to induce apoptosis in neighboring tumor cells that did not express those antigens. These data suggest that small numbers of CTLs could mediate a potent antitumor effect when combined with chemotherapy. In addition, these results provide a strong rationale for combining these modalities for the treatment of patients with advanced cancers.
Combined Targeting of PDK1 and EGFR Triggers Regression of Glioblastoma by Reversing the Warburg Effect
Authors: Kiran Kumar Velpula, Arnima Bhasin, Swapna Asuthkar, Andrew J. Tsung
Journal: Cancer Research (2013)

Glioblastoma multiforme is the most aggressive primary brain tumor in adults. Overexpression of the EGF receptor (EGFR) is recognized as a widespread oncogenic signature in glioblastoma multiforme, but the complexity of its contributions is not fully understood, nor the most effective ways to leverage anti-EGFR therapy in this setting. Hypoxia is known to drive the aggressive character of glioblastoma multiforme by promoting aerobic glycolysis rather than pyruvate oxidation carried out in mitochondria (OXPHOS), a phenomenon termed the Warburg effect, which is a general feature of oncogenesis. In this study, we report that hypoxia drives expression of the pyruvate dehydrogenase kinase (PDK1) and EGFR along with the hypoxia-inducing factor (HIF)-1α in human glioblastoma multiforme cells. PDK1 is a HIF-1-regulated gene and our findings indicated that hypoxia-induced PDK1 expression may promote EGFR activation, initiating a feed-forward loop that can sustain malignant progression. RNAi-mediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased HIF-1α expression, shifting the Warburg phenotype to OXPHOS and inhibiting glioblastoma multiforme growth and proliferation. In clinical specimens of glioblastoma multiforme, we found that immunohistochemical expression of PDK1, EGFR, and HIF-1α were elevated in glioblastoma multiforme specimens when compared with normal brain tissues. Collectively, our studies establish PDK1 as a key driver and candidate therapeutic target in glioblastoma multiforme.
A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure
Authors: Jay N. Cohn, Gianni Tognoni
Journal: New England Journal of Medicine (2001)

Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs. We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure.
Structure-dependent dynamic mechanical behavior of fibrous caps from human atherosclerotic plaques.
Authors: R T Lee, A J Grodzinsky, E H Frank, R D Kamm, F J Schoen
Journal: Circulation (1991)

BACKGROUND Although thrombosis associated with a fissured atherosclerotic plaque is believed to be the most common cause of acute coronary syndromes, the underlying factors that trigger plaque rupture are currently unknown. However, the mechanical behavior of the plaque is probably of critical importance. METHODS AND RESULTS To test the hypothesis that the mechanical properties of a plaque are dependent on its composition and, in particular, that the stiffness of fibrous caps changes within the range of frequencies carried by a physiological pressure wave, the stress-strain relation was studied in 27 fibrous caps and related to the underlying histological structure of the fibrous cap. Fibrous caps were obtained during 14 autopsies from the abdominal aorta and were classified by histological examination as cellular (n = 7), hypocellular (n = 9), or calcified (n = 11). Hypocellular fibrous caps were 1-2 times stiffer than cellular caps (p less than 0.005), and calcified caps were 4-5 times stiffer than cellular caps (p less than 0.005). All 27 fibrous caps demonstrated an increase in stiffness with increasing frequencies of stress ranging from 0.05 to 10 Hz; the increase in stiffness was similar in all three histological classes. CONCLUSIONS We conclude that the stiffness of fibrous caps from human atherosclerotic plaques is related to the underlying histological structure and that the stiffness increases with frequency in the range of physiological heart rates. The protective benefit of beta-adrenergic receptor blocking agents in coronary artery disease may, in part, be related to the frequency dependence of atherosclerotic plaque stiffness.
Changes in Ischemic Tolerance and Effects of Ischemic Preconditioning in Middle-aged Rat Hearts
Authors: Masato Tani, Yukako Suganuma, Hiroshi Hasegawa, Ken Shinmura, Yoko Hayashi, Xiao-dong Guo, Yoshiro Nakamura
Journal: Circulation (1997)

Background Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats. Methods and Results The hearts of young adult rats (12 weeks old: group Y, n=44) and middle-aged rats (50 weeks old: group M, n=44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 20 (group Y, n=22) or 15 (group M, n=22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40.5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14.1; creatine phosphate, 17.0 to 23.1 μmol/g dry wt) and reduced left ventricular end-diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca 2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 μmol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion-induced ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca 2+ release in group M. Conclusions These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.