tbuckley/cabot-search huggingface dataset:
Hemodynamic Effects of Practolol at Rest and during Exercise
Authors: DONALD F. LEON, MARK E. THOMPSON, JAMES A. SHAVER, ROBERT H. MCDONALD
Journal: Circulation (1972)

The effects of practolol, a new beta-adrenergic blocking agent, and propranolol were studied in volunteers. At rest, practolol caused a very small reduction in cardiac index (CI), 190 ml, P &lt; 0.25, and preejection period (PEP) lengthened 3 msec, P &lt; 0.025. In contrast, propranolol caused a reduction in CI of 770 ml, P &lt; 0.001. Heart rate (HR) slowed 10 beats/min, P &lt; 0.001, stroke volume index (SVI) fell 6 ml, P &lt; 0.005, PEP lengthened 16 msec, P &lt; 0.001, and peripheral vascular resistance (PVR) increased 419 dynes-sec-cm –5 , P &lt; 0.001. Practolol reduced the increase in CI caused by an isoproterenol infusion by 65%, P &lt; 0.005, by blocking the increase in HR by 73%, P &lt; 0.05. Practolol also reduced the shortening of PEP and LVET caused by isoproterenol. PVR decreases due to isoproterenol were not blocked by practolol although they were slightly attenuated, P &lt; 0.025. Practolol reduced the increase in CI caused by exercise by 22%, P &lt; 0.05, by blocking the increase in HR by 29%, P &lt; 0.01. Practolol also reduced the increase in tension-time index due to exercise by 25%, P &lt; 0.025. Practolol has little effect on the performance of the normal heart at rest. It does block the cardiac effects of isoproterenol and exercise, largely through chronotropic mechanisms. The reductions in pressure-time relationships with exercise indicate reduced oxygen consumption by the heart, and therefore imply a therapeutic benefit in exercise-induced angina.
THE INFLUENCE OF DENTAL DISEASE ON THE ETIOLOGY OF CERTAIN OCULAR DISTURBANCES.
Authors: WILLIS O. NANCE
Journal: JAMA (1904)

That dental caries and its allied processes figure to a considerable degree in the etiology of certain ocular disorders seems to have been generally recognized by those who have made this subject a matter of careful observation. Difficult early dentition, also, has long been considered in the same light, and as far back as 1824, Travers<sup>1</sup>called attention to strabismus as a symptom sometimes arising from this cause. Galezowski,<sup>2</sup>the eminent French ophthalmologist, has, for several decades, enthusiastically supported the theory of dental causation of various eye troubles, and many of the ablest contributions to the literature of this subject are from his pen. So strongly imbued with the teachings of his confrére was Weinberg,<sup>3</sup>that he expressed the belief that during a nine months' dispensary service he saw 188 cases of ocular disturbance dependent on morbid dental changes. Henry Power,<sup>1</sup>in 1883, read a meritorious paper on the subject
Hypsarrhythmia and Infantile Spasms
Authors: B. D. Bower, P. M. Jeavons
Journal: BMJ (1965)

<h3>Background and importance</h3> Critical care pharmacists have demonstrated their contribution to the management of drug therapy and impact on patient and medication safety. Traditionally, the functions of the clinical pharmacist in the intensive care unit (ICU) of our hospital were based on pharmaceutical interventions (PIs) concerning parenteral nutrition (PN). Currently, a computerised physician order entry (CPOE) system has been implemented. This system reduces the incidence of medication errors and allows pharmaceutical validation. <h3>Aim and objectives</h3> To analyse the evolution in the number of PIs before and after implementation of the CPOE; to describe the type of PIs carried out by clinical pharmacists after CPOE implementation; and to assess the degree of acceptance by ICU physicians. <h3>Material and methods</h3> A 2 month descriptive and prospective study was conducted between 1 January and 28 February 2020 in an 18 bed ICU of a tertiary teaching hospital, 3 months after CPOE implementation. Every type of PI and degree of acceptance were recorded. Total PIs recorded were compared with those recorded in the same period of time before implementation of the CPOE (between 1 July and 31 August 2020). <h3>Results</h3> During the current study period, 227 patients were admitted to the ICU, and 366 PIs were recorded. PIs increased by 173% compared with the previous study period before the implementation of CPOE (232 patients, 134 PIs). Regarding the number of PIs during the current study period, 25.4% were related to PN prescriptions, 8.4% were related to antimicrobial stewardship programme, 5.7% were related to optimising drug therapy, 3.3% were related to route of administration, 4.6% were related to incorrect drug based on the indication, 2.7% were related to therapeutic drug monitoring and 46.4% were related to fluid therapy. 91% of PIs were accepted by the ICU staff. <h3>Conclusion and relevance</h3> CPOE in the ICU promoted the pharmacist’s participation in improving the safety of medical prescriptions by increasing the number of accepted PIs. The high number of interventions related to fluid therapy was highlighted. We consider it necessary to start corrective measures regarding this aspect, such as the preparation of prescription protocols, training talks, etc. <h3>References and/or acknowledgements</h3> <h3>Conflict of interest</h3> No conflict of interest
Enhanced Gene Transfer to Mouse Dendritic Cells Using Adenoviral Vectors Coated with a Novel Adapter Molecule
Authors: Alexander V Pereboev, Jill M Nagle, Mikhail A Shakhmatov, Pierre L Triozzi, Qiana L Matthews, Yosuke Kawakami, David T Curiel, Jerry L Blackwell
Journal: Molecular Therapy (2004)

Adenovirus (Ad)-mediated transduction of dendritic cells (DC) is inefficient because of the lack of the primary Ad receptor, CAR. DC infection with Ad targeted to the CD40 results in increased gene transfer. The current report describes further development of the CD40-targeting approach using an adapter molecule that bridges the fiber of the Ad5 to CD40 on mouse DC. The adapter molecule, CFm40L, consists of CAR fused to mouse CD40 ligand via a trimerization motif. A stable cell line that secretes CFm40L at high levels was generated. Gene transfer to mouse bone marrow-derived DC (mBMDC) using CFm40L-targeted Ad was over 4 orders of magnitude more efficient than that for the untargeted Ad5. Gene transfer was achieved to over 70% of the mBMDC compared to undetectable transduction using untargeted Ad5. In addition to dramatically enhanced gene transfer, the CFm40L-targeted Ad5 induced phenotypical maturation and upregulated IL-12 expression. Most importantly, the CFm40L-targeted Ad5 elicited specific immune response against a model antigen in vivo. The results of this study demonstrate that Ad-mediated gene transfer to DC can be significantly enhanced using nonnative transduction pathways, such the CD40 pathway, which may have important applications in genetic vaccination for cancer and infectious diseases.
Morbid Obesity and Related Health Risks
Authors: JOHN G. KRAL
Journal: Annals of Internal Medicine (1985)

Persons 45.4 kg (100 lb) or more above desirable weight have exponential increases in mortality and serious morbidity compared with normal persons. The presence of a complication or an independent coronary risk factor along with obesity increases the mortality further. Among the "threshold conditions" that appear at a critical level of body weight (60% or more above desirable weight), the most important are sudden unexplained death, ventilatory disorders, circulatory congestion, and functional limitations in activities of daily living. Recent epidemiologic data on extreme obesity and data on cardiac dysfunction show impaired quality of life in young, morbidly obese patients. Because of the malignant nature of morbid obesity and the inability to achieve and maintain sufficient weight reduction by non-surgical means, surgery is justified in this population.
Growth-Inhibition Effects of Oleic Acid, Linoleic Acid, and Their Methyl Esters on Transplanted Tumors in Mice
Authors: Y.-P. Zhu, Z.-W. Su, C.-H. Li
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Growth-Inhibition Effects of Oleic Acid, Linoleic Acid, and Their Methyl Esters on Transplanted Tumors in Mice Get access You-Ping Zhu, You-Ping Zhu * Department of Pharmacognosy, School of Pharmacy, Second Military Medical UniversityShanghai, China *Correspondence to: Dr. You-Ping Zhu, Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guo He Rd., Shanghai 200433, China. Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhong-Wu Su, Zhong-Wu Su Department of Pharmacognosy, School of Pharmacy, Second Military Medical UniversityShanghai, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Chen-Hu Li Chen-Hu Li Department of Pharmacognosy, School of Pharmacy, Second Military Medical UniversityShanghai, China Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 17, 6 September 1989, Pages 1302–1306, https://doi.org/10.1093/jnci/81.17.1302 Published: 06 September 1989 Article history Received: 30 May 1989 Accepted: 12 June 1989 Published: 06 September 1989
Heyde's Syndrome Incidence and Outcome in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Cosmo Godino, Ludovica Lauretta, Anna Giulia Pavon, Antonio Mangieri, Giacomo Viani, Alaide Chieffo, Stefano Galaverna, Azeem Latib, Matteo Montorfano, Alberto Cappelletti, Francesco Maisano, Ottavio Alfieri, Alberto Margonato, Antonio Colombo
Journal: Journal of the American College of Cardiology (2013)
Retrograde Pre-excitation
Authors: ONKAR S. NARULA
Journal: Circulation (1974)

The purpose of this report was to compare antegrade (atrioventricular [A-V]) and retrograde (ventriculoatrial [V-A]) conduction times in 124 consecutive patients who exhibited bidirectional conduction during diagnostic studies where His bundle recordings were obtained. None of these patients had any evidence of antegrade pre-excitation. The mean age was 64 ± 13 (range 32-89 years). The QRS complex was abnormal (≧ 0.11 sec) in 46 patients. The control mean P-R, A-H, and H-V times were 170 ± 37, 80 ± 21, 49 ± 8 msec, respectively. The A-V and V-A times were measured from local bipolar right ventricular (RV) and right atrial (RA) electrograms obtained via pacing catheters placed in the high RA and RV apex. Both RA and RV were paced at identical cycle lengths and the rate was progressively increased until block developed or to a cycle length of 400-330 msec. The V-A time was longer than A-V in 45 (group A), equal in 11 (group B), and shorter in 68 patients. Of the latter 68 patients (group C) in 49 V-A time was 172 ± 36 as compared to 197 ± 38 msec for A-V time, and while the interval lengthened at higher pacing rates, it remained shorter than A-V time throughout (197 ± 40 versus 261 ± 51 msec). In the remaining 19 patients (group D) the V-A was not only shorter than A-V (176 ± 27 versus 207 ± 49 msec) but remained unchanged up to the highest paced rates, whereas A-V time progressively lengthened 269 ± 81 msec). In group D a constant V-A time in all probability is indicative of retrograde impulse transmission through tissue other than the A-V node, i.e., bypass pathways functioning only in a retrograde direction. Progressively increasing A-V and V-A times in groups A to C suggest bidirectional conduction through a single common pathway. Our data demonstrate that: 1) V-A is less often longer (35%) and more often shorter (56%) than A-V; 2) In some patients retrograde pre-excitation and V-A may occur through bypass pathways, functional in the retrograde direction only. These findings may be of clinical significance.
The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model
Authors: Terry C. Major, David O. Brant, Charles P. Burney, Kagya A. Amoako, Gail M. Annich, Mark E. Meyerhoff, Hitesh Handa, Robert H. Bartlett
Journal: Biomaterials (2011)
Biological Response Modifiers May Yield a New Class of Drugs to Treat Arthritis
Authors: Andrew A. Skolnick
Journal: JAMA (1997)

ENCOURAGING results from phase II clinical trials suggest that 3 genetically engineered agents could become the first of a new class of pharmaceuticals for treating rheumatoid arthritis. The results of the randomized, placebocontrolled trials were reported at the 1996 Scientific Meeting of the American College of Rheumatology (ACR) in Orlando, Fla. Unlike current therapies, the new agents are aimed at specific targets in the immune system. They work by blocking the biological processes that drive bone and cartilage destruction in the joints of patients with rheumatoid arthritis. While nonsteroidal anti-inflammatory drugs reduce the pain and swelling of arthritis, they do not prevent the progressive destruction of the joints. More potent drugs, known as disease modifiers, can retard disease progression in some patients. However, these drugs take a long time to yield clinical improvement and often produce adverse reactions that can be worse than the arthritis—such as osteoporosis from corticosteroids (<i>JAMA</i>
Abstract 3684: Targeting Aurora kinase in peripheral T-cell non-Hodgkin's lymphomas
Authors: Daruka Mahadevan, Wenqing Qi, Xiaobing Liu, Laurence S. Cooke, Amit Agarwal, Daniel O. Persky, Thomas P. Miller
Journal: Cancer Research (2012)

Abstract Aurora kinases (A and B) are oncogenic serine/threonine (S/T) kinases that play central roles in the mitotic phase of the eukaryotic cell cycle. Over-expression of Auroras during dysregulated cell cycling and their aberrant activation over-rides mitotic and spindle check points leading to anueploidy in many human cancers make Auroras attractive therapeutic targets. Gene expression profiling in mantle cell lymphoma [MCL] have shown the Auroras are over-expressed and is a poor prognostic marker within the ‘proliferative’ signature. PTCL (NOS) are a heterogeneous group of rare non-Hodgkin's lymphomas (NHL) derived from activated CD4+ or CD8+ T cells. PTCL and anaplastic large cell lymphoma (ALCL) both of T-cell phenotype and ALK negative have an aggressive clinical course with an inferior event free and overall survival relative to B-cell NHL counterparts. The biological explanation for the difference is unknown. Patients with PTCL have a poor prognosis due to a very aggressive disease course coupled to a lack of effective therapies. Therefore, the development of novel and effective treatments based on biologically validated targets is urgently needed for this disease. We hypothesized and investigated that (1). Auroras are over-expressed in human PTCL-NOS, (2). Aurora ATP-site small molecule inhibitor (SMI) is effective in inhibiting cell proliferation and promoting apoptosis in cell culture and (3). Aurora SMI will be safe and effective in treating patients with relapsed aggressive T-cell NHL in early phase clinical trials. In this study, we demonstrate that both aurora A and B are highly over-expressed in PTCL patients and cell lines. MLN8237 (alisertib), an ATP-site small molecule inhibitor of Aurora A had potent activity in inhibiting phosphorylation of Aurora A and histone H3 in PTCL cell lines. Cells treated with MLN8237 exhibited endoreduplication confirming the mechanism of action of an Aurora inhibitor. Also, treatment of PTCL cell lines with MLN8237 induced apoptosis in a dose and time dependent manner (flow cytometry and PARP-cleavage) and inhibited cell proliferation with an IC50 &amp;lt; 0.1µM. Preliminary data from a phase II clinical trial using single-agent MLN8237 in patients with relapsed refractory aggressive NHL has demonstrated notable activity with 4 confirmed responses in 6 evaluable PTCL patients. Cytokine profiling on day 1 (pre-treatment) and day 8 (post-treatment) showed a profile consistent with aurora A activity. Together the data suggest inhibition of Auroras offers a promising treatment strategy for patients with aggressive T-cell NHL [Funded by the Lymphoma SPORE, P50 CAB0805501A1]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3684. doi:1538-7445.AM2012-3684
Interaction of hepatitis C virus core protein with retinoid X receptor α modulates its transcriptional activity
Authors: Takeya Tsutsumi, Tetsuro Suzuki, Takashi Shimoike, Ryosuke Suzuki, Kyoji Moriya, Yoshizumi Shintani, Hajime Fujie, Yoshiharu Matsuura, Kazuhiko Koike, Tatsuo Miyamura
Journal: Hepatology (2002)

Hepatic steatosis and hepatocellular carcinoma (HCC) are common and serious features of hepatitis C virus (HCV) infection, and the core protein has been shown to play distinct roles in the pathogenesis. Here we report the direct interaction of HCV core protein with retinoid X receptor α (RXRα), a transcriptional regulator that controls many aspects of cell proliferation, differentiation, and lipid metabolism. The core protein binds to the DNA-binding domain of RXRα, leading to increase the DNA binding of RXRα to its responsive element. In addition, RXRα is activated in cells expressing the core protein as well as in the livers of the core-transgenic mice that would develop hepatic steatosis and HCC later in their lives. Using promoter genes of cellular retinol binding protein II (CRBPII) and acyl-CoA oxidase as reporters, we also show that the expression of the core protein enhances the transcriptional activity regulated by the RXRα homodimer as well as by the heterodimer with peroxisome proliferator activated receptor α. Furthermore, expression of the CRBPII gene is also up-regulated in the livers of HCV core-transgenic mice. In conclusion, these results suggest that modulation of RXRα-controlled gene expression via interaction with the core protein contributes to the pathogenesis of HCV infection.
More Medical Education
Authors: BURTON A. WAISBREN
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 April 1972More Medical EducationBURTON A. WAISBREN JR.BURTON A. WAISBREN JR.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-4-674_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Because America's system of medical education has failed to produce an adequate number of doctors, it is time to explore new and more efficient ways of training them. I wish to propose a system of medical education that will make maximum use of both existing facilities and available federal funds.The first step would be to expand the undergraduate premedical curriculum to include the preclinical subjects that are presently taught in medical schools. Universities without affiliated medical schools often have excellent departments of chemistry and biology, as well as ample laboratory space. The addition of pathology and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1972Volume 76, Issue 4Page: 674-674KeywordsMedical educationResearch laboratoriesUndergraduates Issue Published: 1 April 1972 PDF downloadLoading ...
Standardised mortality rates in females and males with COPD and asthma
Authors: T. Ringbaek, N. Seersholm, K. Viskum
Journal: European Respiratory Journal (2005)

Mortality studies of males and females with chronic obstructive pulmonary disease (COPD) and asthma have suggested that females have a poorer prognosis than males, but the results are either not unanimous or based on poorly characterised patients. The current study analysed the mortality of 279 asthma patients and 869 COPD patients, who were seeking pension due to disability, and compared mortality rates with expected rates derived from the general population. The mean follow-up period was 13.3 yrs (range 2.5–22.4 yrs) during which time 96 (34.4%) and 671 (77.2%) deaths were identified among asthma and COPD patients, respectively. The average age at study entry was 46.8 and 56.6 yrs, and the average forced expiratory volume in one second (FEV 1 ) was 68.8 and 44.1 % predicted in the two diagnostic groups. After adjustment for predictors of survival (age, FEV 1 % predicted, chronic bronchitis, body mass index, smoking status, oral prednisolone, ischaemic heart disease, and cor pulmonale), the relative risk of death was 1.21 (95% confidence interval: 0.77–1.89) and 0.98 (0.83–1.16) in females compared with males, in asthma and COPD patients, respectively. The standardised mortality rate (SMR) for males was 1.54 (1.10–2.09) and 2.7 (2.5–3.0), and for females 1.91 (1.44–2.49) and 4.8 (4.2–5.4), in asthma and COPD patients, respectively. Direct comparison of the SMR of males and females showed that females had higher mortality than males, with a rate ratio of 1.24 (0.82–1.84) and 1.8 (1.5–2.0), in asthma and COPD patients, respectively. Poisson regression analysis with control for the confounders did not change this result. Females and males with the same level of obstructive lung disease appear to have the same level of mortality. However, using standardised mortality rates, females have a higher mortality than males, suggesting that the protective effect of being female is lost in chronic obstructive pulmonary disease patients.
Grants Focus on Leveraging Biomedical Big Data
Authors: Tracy Hampton
Journal: JAMA (2014)

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