tbuckley/cabot-search huggingface dataset:
ETHAVERINE IN THE TREATMENT OF ANGINA PECTORIS
Authors: Carl M. Voyles
Journal: JAMA (1953)

In laboratory animals papaverine acts as a potent coronary vasodilator drug.<sup>1</sup>Studies<sup>2</sup>indicate that ethaverine (6,7-diethoxy-1-[3,4-diethoxybenzyl] isoquinoline), the ethyl analogue of papaverine, is a general visceral and vascular spasmolytic agent. In recent experiments concerning the coronary blood flow of quickly isolated, beating rabbit hearts, ethaverine has been shown to be equal to papaverine in peak potency but of more durable action, so that in total effect summed up over time it is more effective.<sup>3</sup>Ethaverine has the advantage of not being classified as a narcotic under the Harrison Act.<sup>4</sup>The toxicity of ethaverine is roughly one-third that of papaverine, and large doses have been given in man without untoward effect. In a previous study,<sup>5</sup>16 patients with relatively stable angina pectoris were given ethaverine over periods of 4 to 20 weeks, followed by placebo therapy for corresponding periods. Seven of these 16 patients experienced marked
Solving Our Primary Care Crisis by Retraining Specialists to Gain Specific Primary Care Competencies
Authors: George D. Lundberg
Journal: JAMA (1993)

ABSTRACT That this country now has a full-blown crisis in its primary care physician work force is hardly disputed.1-3 Simply stated, other developed industrial countries for many years have practiced medicine with roughly 50% of physicians in primary care and 50% in specialties and subspecialties.4 In the United States, however, we train and employ about 32% primary care physicians (general practitioners, family physicians, general internists, general pediatricians, and some obstetrician-gynecologists and emergency medicine physicians) and about 68% specialists and subspecialists.4 Health indicators show that comparison countries do as well as or better than the United States at providing care at much lower cost, whether cost is measured as the amount spent per capita per year or as a percentage of the gross national product. If that news isn't bad enough, the situation in the United States is rapidly getting worse. The percentage of physicians graduating from US medical
Determining the Null Model for Detecting Adaptive Convergence from Genomic Data: A Case Study using Echolocating Mammals
Authors: Gregg W.C. Thomas, Matthew W. Hahn
Journal: Molecular Biology and Evolution (2015)

Convergent evolution occurs when the same trait arises independently in multiple lineages. In most cases of phenotypic convergence such transitions are adaptive, so finding the underlying molecular causes of convergence can provide insight into the process of adaptation. Convergent evolution at the genomic level also lends itself to study by comparative methods, although molecular convergence can also occur by chance, adding noise to this process. Parker et al. studied convergence across the genomes of several mammals, including echolocating bats and dolphins (Parker J, Tsagkogeorga G, Cotton JA, Liu Y, Provero P, Stupka E, Rossiter SJ. 2013. Genome-wide signatures of convergent evolution in echolocating mammals. Nature 502:228–231). On the basis of a null distribution of site-specific likelihood support (SSLS) generated using simulated topologies, they concluded that there was evidence for genome-wide adaptive convergence between echolocating taxa. Here, we demonstrate that methods based on SSLS do not adequately measure convergence, and reiterate the use of an empirical null model that directly compares convergent substitutions between all pairs of species. We find that when the proper comparisons are made there is no surprising excess of convergence between echolocating mammals, even in sensory genes.
Firearm Injury Prevention
Authors: Frederick Adolf Paola
Journal: Annals of Internal Medicine (1998)

Letters15 August 1998Firearm Injury PreventionFrederick Adolf Paola, MD, JDFrederick Adolf Paola, MD, JDUniversity of South Florida College of Medicine; Tampa, FL 33612Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-4-199808150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Cassel and colleagues' article [1] left me wondering about the importance of some physicians saying that physicians should talk to patients about guns.Did the respondents who said that physicians should talk to patients about guns truly believe this? If they did, why did so few actually do so? Were they asked about this discrepancy? Although one could hypothesize explanations that would not invalidate the authors' conclusion, one could also imagine respondents simply giving the answer they thought the authors wanted.Even if it were established that the respondents believed what they reported, what will have been ...References1. Cassel CK, Nelson EA, Smith TW, Schwab CW, Barlow B, Gary NE. Internists' and surgeons' attitudes toward guns and firearm injury prevention. Ann Intern Med. 1998; 128:224-30. Google Scholar2. Davidoff F. Reframing gun violence [Editorial]. Ann Intern Med. 1998; 128:234-5. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of South Florida College of Medicine; Tampa, FL 33612 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByYes, You Can: Physicians, Patients, and FirearmsGaren J. Wintemute, MD, MPH, Marian E. Betz, MD, MPH, and Megan L. Ranney, MD, MPH 15 August 1998Volume 129, Issue 4Page: 336KeywordsAlcoholismBehaviorDomestic violenceFirearm injuries Issue Published: 15 August 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 3125: EGFRvIII translocates to the nucleus and regulates gene transcription with STAT5
Authors: Khatri Latha, Vaibhav Chumbalkar, Ming Li, YeoHyeon Hwang, Anupama Gururaj, Rebecca Maywald, Sumana Dakeng, Lixia Dao, Keith Baggerly, Raymond Sawaya, Webster Cavenee, Frank Furnaru, Oliver Bögler
Journal: Cancer Research (2010)

Abstract Dysregulation of receptor tyrosine kinases is a major contributor to cancer, including glioblastoma, where amplification and mutation of epidermal growth factor receptor (EGFR) is common. The most common mutation is in-frame deletion of exons 2-7, known as EGFRvIII, EGFR* or ΔEGFR. EGFRvIII confers enhanced tumorigenicity on glioma cells in vivo, reducing apoptosis and increasing proliferation. EGFRvIII signals constitutively and at approximately 5-to-10-fold lower intensity than wild-type. We are investigating the pathways that are preferentially activated by EGFRvIII, using a phosphotyrosine-directed, mass spectrometry-based shotgun phosphoproteomics approach in two different cell lines, LNZ308 (PTEN null) and LN428 (PTEN wt). We identified 433 proteins with 772 peptides out of which 249 proteins corresponding to 354 peptides showed tyrosine phosphorylation. Statistical analysis revealed several signals that were prevalent in EGFRvIII expressing glioma cells, including phosphorylation of STAT5, Gab1 and MIG6. Identification of STAT5 as a target of EGFRvIII prompted an investigation of whether EGFRvIII is active in the nucleus. We have identified EGFRvIII associated with phosphorylated STAT5 on chromatin, and capable of activating the expression of STAT5 target genes, including Aurora A kinase, which positively regulate glioblastoma malignancy. STAT5 promotes expression of the EGFRvIII target gene Bcl-XL, and knockdown of STAT5 reduces the transformation induced by EGFRvIII. Furthermore, we have mutated signals in EGFRvIII that regulate nuclear localization, and are examining the impact of these on its ability to promote tumor growth. In a related study we have used artificial receptor dimerization, mediated by technology from Ariad Pharmaceuticals, to enhance the EGFRvIII signal. A chimeric version of EGFRvIII was created, in which the receptor was fused N-terminally with two FKBP-F36V domains that could be activated by the chemical inducer of dimerization, AP20187. This has resulted in a more oncogenic form of EGFRvIII that emits a stronger signal, and we are using this to deepen our phosphoproteomics analysis to seek additional preferential targets of EGFRvIII action, which will be reported. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3125.
Patient Access to Information on Clinicians Infected With Blood-Borne Pathogens
Authors: Norman Fost
Journal: JAMA (2000)

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
Asthma control in the Asia-Pacific region: The asthma insights and reality in Asia-Pacific study
Authors: Christopher K.W. Lai, Teresita S. de Guia, You-Young Kim, Sow-Hsong Kuo, Amartya Mukhopadhyay, Joan B. Soriano, Pham Long Trung, Nan Shan Zhong, Norzila Zainudin, B.M.Z. Zainudin
Journal: Journal of Allergy and Clinical Immunology (2003)
IMPACT OF THE ETIOLOGY OF MITRAL REGURGITATION ON CALCULATION OF REGURGITANT VOLUME USING THE PROXIMAL FLOW CONVERGENCE METHOD
Authors: Byung Joo Sun, Jeong Yoon Jang, Seungmo Kang, Yun-Sil Choi, Min Kyoung Jang, Deok Jin Seo, Dae-Hee Kim, Jong-Min Song, Duk-Hyun Kang, Jae-Kwan Song
Journal: Journal of the American College of Cardiology (2013)
Morphine in a Patent Medicine
Authors: P. B. Woolley
Journal: BMJ (1947)

Many Russians in my care during the war, even those who had been wounded before capture, awaited their return home with extreme terror.Why ?I agree that social security, whatever it may mean, has tended to reduce effort for the reasons advanced by Dr. Crichton-Miller.Many economists suggest that the economic basis for this social security is crumbling, so we may soon see the next phase developing.-Iam, etc.,
Is the time constant of the pulmonary circulation truly constant?
Authors: Robert Naeije, Marion Delcroix
Journal: European Respiratory Journal (2014)

From the authors: 

J.C. Grignola points out that the product of pulmonary vascular resistance by pulmonary vascular compliance, or time constant (RC time) of the pulmonary circulation is not truly constant, and that this impacts on the pulsatile component ( W osc) of right ventricular hydraulic load ( W tot).

He is right. But the question is, by how much? In the experimental study by Pagnamenta et al. [1], pulmonary hypertension induced by ensnarement of the pulmonary arteries, to mimic purely proximal chronic thromboembolic pulmonary hypertension (CTEPH), was associated with a decrease in RC time from 0.5 s to 0.3 s, while microembolism to mimic purely distal obstruction, like in pulmonary arterial hypertension …
Clostridial toxins
Authors: Numan Oezguen, Trevor D. Power, Petri Urvil, Hanping Feng, Charalabos Pothoulakis, Jonathan S. Stamler, Werner Braun, Tor C. Savidge
Journal: Gut Microbes (2012)

The current global outbreak of Clostridium difficile infection exemplifies the major public health threat posed by clostridial glucosylating toxins. In the western world, C. difficile infection is one of the most prolific causes of bacterial-induced diarrhea and potentially fatal colitis. Two pathogenic enterotoxins, TcdA and TcdB, cause the disease. Vancomycin and metronidazole remain readily available treatment options for C. difficile infection, but neither is fully effective as is evident by high clinical relapse and fatality rates. Thus, there is an urgent need to find an alternative therapy that preferentially targets the toxins and not the drug-resistant pathogen. Recently, we addressed these critical issues in a Nature Medicine letter, describing a novel host defense mechanism for subverting toxin virulence that we translated into prototypic allosteric therapy for C. difficile infection. In this addendum article, we provide a continued perspective of this antitoxin mechanism and consider the broader implications of therapeutic allostery in combating gut microbial pathogenesis.
Embolic Protection and Platelet Inhibition During Renal Artery Stenting
Authors: Christopher J. Cooper, Steven T. Haller, William Colyer, Michael Steffes, Mark W. Burket, William J. Thomas, Robert Safian, Bhagat Reddy, Pamela Brewster, Mary Ann Ankenbrandt, Renu Virmani, Eric Dippel, Krishna Rocha-Singh, Timothy P. Murphy, David J. Kennedy, Joseph I. Shapiro, Ralph D. D'Agostino, Michael J. Pencina, Sadik Khuder
Journal: Circulation (2008)

Background— Preservation of renal function is an important objective of renal artery stent procedures. Although atheroembolization can cause renal dysfunction during renal stent procedures, whether adjunctive use of embolic protection devices or glycoprotein IIb/IIIa inhibitors improves renal function is unknown. Methods and Results— One hundred patients undergoing renal artery stenting at 7 centers were randomly assigned to an open-label embolic protection device, Angioguard, or double-blind use of a platelet glycoprotein IIb/IIIa inhibitor, abciximab, in a 2×2 factorial design. The main effects of treatments and their interaction were assessed on percentage change in Modification in Diet in Renal Disease–derived glomerular filtration rate from baseline to 1 month using centrally analyzed creatinine. Filter devices were analyzed for the presence of platelet-rich thrombus. With stenting alone, stenting and embolic protection, and stenting with abciximab alone, glomerular filtration rate declined ( P &lt;0.05), but with combination therapy, it did not decline and was superior to the other allocations in the 2×2 design ( P &lt;0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0±27% versus −10±20%; P &lt;0.05), embolic protection was not (−1±28% versus −10±20%; P =0.08). An interaction was observed between abciximab and embolic protection ( P &lt;0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% ( P &lt;0.01). Conclusions— Renal artery stenting alone, stenting with embolic protection, and stenting with abciximab were associated with a decline in glomerular filtration rate. An unanticipated interaction between Angioguard and abciximab was seen, with combination therapy better than no treatment or either treatment alone.
Induced sputum eicosanoids during aspirin bronchial challenge of asthmatic patients with aspirin hypersensitivity
Authors: L. Mastalerz, N. Celejewska-Wójcik, K. Wójcik, A. Gielicz, R. Januszek, A. Cholewa, P. Stręk, M. Sanak
Journal: Allergy (2014)

Altered metabolism of eicosanoids is a characteristic finding in aspirin-exacerbated respiratory disease (AERD). Bronchial challenge with lysyl-aspirin can be used as a confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions.To investigate the influence of inhaled lysyl-aspirin on sputum supernatant concentration of eicosanoids during the bronchial challenge test. Subjects with asthma hypersensitive to nonsteroidal anti-inflammatory drugs were compared with aspirin-tolerant asthmatic controls.Induced sputum was collected before and following bronchial challenge with lysyl-aspirin. Sputum differential cell count and sputum supernatant concentrations of selected lipoxygenases products: 5-,12-,15-hydroxyeicosatetraenoic acid, cysteinyl leukotrienes, leukotriene B4 , 11-dehydro-thromboxane B2 , and prostaglandins E2 , D2 , and F2α and their metabolites, were measured using validated methods of chromatography-mass spectrometry.Aspirin precipitated bronchoconstriction in all AERD subjects, but in none of the aspirin-tolerant asthmatics. Phenotypes of asthma based on the sputum cytology did not differ between the groups. Baseline sputum eosinophilia correlated with a higher leukotriene D4 (LTD4 ) and leukotriene E4 (LTE4 ) concentrations. LTC4 , PGE2 , and 11-dehydro-TXB2 did not differ between the groups, but levels of LTD4 , LTE4 , and PGD2 were significantly higher in AERD group. Following the challenge, LTD4 and LTE4 increased, while PGE2 and LTB4 decreased in AERD subjects only.During the bronchial challenge, decrease in PGE2 and its metabolite is accompanied by a surge in bronchoconstrictory cysteinyl leukotrienes produced at the expense of LTB4 in AERD subjects. Bronchial PGE2 inhibition in AERD seems specific and sensitive to a low dose of aspirin.
Abstract 3553: Scutellaria barbata inhibits angiogenesis through downregulation of HIF-1 α expression in lung tumor
Authors: Che-Hsin Lee, Yu-Ting Shen, Chao-Liang Wu, N-H Chow, Ai-Li Shiau
Journal: Cancer Research (2011)

Abstract Hypoxia, a hallmark of many solid tumors, is associated with angiogenesis and tumor progression. Hypoxia-inducible factor-1 (HIF-1) plays a significant role in tumor angiogenesis. In this study, we constructed a selective platform to screen the traditional Chinese medicine as anti-angiogenic agent. We examined the molecular mechanism by which Scutellaria barbata (S. barbata) regulates HIF-1-dependent expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. Hypoxia stimulated with the HIF-1 expression promotes angiogenesis by increasing VEGF expression and secretion. Herein, the expression of VEGF was decreased by treatment with S. barbata in tumor cells. Meanwhile, S. barbata reduced the migration and proliferation of endothelial cells under hypoxic condition. S. barbata inhibited the expression of HIF-1α, as well as phosphorylated their upstream signal mediators AKT. S. barbata significant retarded the tumor growth by 56% in vivo and immunohistochemical studies in the tumors revealed decreased intratumoral microvessel density. These results suggest that the traditional Chinese medicine therapy using S. barbata, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors. 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 3553. doi:10.1158/1538-7445.AM2011-3553
Measurement of Polybrominated Diphenyl Ethers and Metabolites in Mouse Plasma after Exposure to a Commercial Pentabromodiphenyl Ether Mixture
Authors: Xinghua Qiu, Minerva Mercado-Feliciano, Robert M. Bigsby, Ronald A. Hites
Journal: Environmental Health Perspectives (2007)

Previous studies have shown that polybrominated diphenyl ethers (PBDEs) behave as weak estrogens in animal and cell culture bioassays. In vivo metabolites of PBDEs are suspected to cause these effects.To identify candidate metabolites, mouse plasma samples were collected after continuous oral and subcutaneous exposure to DE-71, a widely used commercial pentabromodiphenyl ether product, for 34 days.Samples were extracted, separated into neutral and phenolic fractions, and analyzed by gas chromatographic mass spectrometry.In the plasma samples of orally treated animals, 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153) represented 52% of total measurable PBDEs, whereas it represented only 4.3% in the DE-71 mixture. This suggested that BDE-153 was more persistent than other congeners in mice. Several metabolites were detected and quantitated: 2,4-dibromophenol, 2,4,5-tribromophenol, and six hydroxylated PBDEs. The presence of the two phenols suggested cleavage of the ether bond of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), respectively. The hydroxylated (HO)-PBDEs might come from hydroxylation or debromination/hydroxylation. Among the quantitated hydroxylated metabolites, the most abundant was 4-HO-2,2',3,4'-tetra-BDE, which suggested that there was a bromine shift during the hydroxylation process. para-HO-PBDEs have been proposed to behave as endocrine disruptors.THERE SEEM TO BE THREE METABOLIC PATHWAYS: cleavage of the diphenyl ether bond, hydroxylation, and debromination/hydroxylation. The cleavage of the diphenyl ether bond formed bromophenols, and the other two pathways formed hydroxylated PBDEs, of which para-HO-PBDEs are most likely formed from BDE-47. These metabolites may be the most thyroxine-like and/or estrogen-like congeners among the HO-PBDEs.
Immune interferon in serum and synovial fluid in rheumatoid arthritis and related disorders.
Authors: M DeGre, O J Mellbye, O Clarke-Jenssen
Journal: Annals of the Rheumatic Diseases (1983)

Moderate titres of antiviral activity were demonstrated in 48-58% of sera obtained from patients suffering from seropositive and seronegative rheumatoid arthritis (RA), psoriatic arthritis, Reiter's syndrome, ankylosing spondylitis, and juvenile rheumatoid arthritis.Sera from blood donors and from patients with various noninflammatory diseases were positive in 16% of cases.The activity was species-specific, mediated by the homologous cells, and destroyed by treatment with trypsin and exposure to pH 2. Antibodies against human IFN-a did not neutralise the activity.These characteristics are compatible with those of IFN--y or immune interferon.Neither the presence nor the titre of IFN was correlated with disease activity defined by concentra- tion of C-reactive protein, C3 concentration, and erythrocyte sedimentation rate.IFN--y was present in 4 of 10 synovial fluids from patients with RA.The titre in one of these was higher than in the corresponding serum, indicating local production in the rheumatoid joint.Stimulation of lymphocyte blastogenesis and proliferation may be accompanied by induction of inter- feron (IFN).Such stimuli include either nonspecific mitogens' or cellular immune reactions by specific antigens.2The immune-specific nature of the response has been demonstrated.4Similarly, IFN production can be shown in mixed cultures of tumour cells and lymphocytes5 and tumour cells and macro- phages.6The IFN produced by the stimulated lymphocytes differs in several respects from the clas- sical virus-induced interferons, for instance in sen- sitivity to treatment at low pH, stability at 56°C, cross-species activity, and antigenic specificity.The former type is termed IFN--y, previously called 'im- mune' or type II, in contrast to the virus-induced IFN-a and IFN-,B, previously called type I inter- ferons.Following the original observation that IFN-y are produced in vivo in response to mitogens and specific antigens it has been reported that circulating IFN--y can be detected in patients with autoimmune diseases as rheumatoid arthritis, systemic lupus erythematosus, and Sjogren's syndrome.7In the present communication we confirm and extend these obser- vations, which give further evidence for cellular