tbuckley/cabot-search huggingface dataset:
The Action of Acetylcholine and Epinephrine on the Cellular Membrane Potentials and Contractility of Rat Atrium
Authors: J. LEYDEN WEBB, PHILIP B. HOLLANDER
Journal: Circulation Research (1956)

Acetylcholine diminished the developed tension of contraction in rat atria; simultaneously there was a slight increase in resting potential, no appreciable change in action potential, a decrease in the rate of conduction, only a minor alteration of the form of contraction, and, most strikingly, a decrease in the duration of the action potential or the area enclosed by it. The rate of repolarization subsequent to the action potential was markedly accelerated. Epinephrine, in general, produced the opposite effects and slowed the repolarization rate as it augmented atrial contraction. Cholinesterase does not seem to play a direct role in cardiac membrane potentials or ion transfer since physostigmine had no effect of its own on the electric manifestations. Certain aspects of the mechanisms involved are discussed.
Identification of myocardial infarction by contrast echocardiography using a new transpulmonary agent - NC100100: comparison of anterior vs. posterior, and patchy vs. solid necrosis
Authors: N. Masani, J. Yao, Q.L. Cao, E. Avelar, M. Vannan, N. Pandian
Journal: Journal of the American College of Cardiology (1998)
Effect of High-Altitude Exposure in the Elderly
Authors: Benjamin D. Levine, Julie H. Zuckerman, Christopher R. deFilippi
Journal: Circulation (1997)

Background More than 5 million people/year over age 60 visit high altitude, which may exacerbate underlying cardiac or pulmonary disease. We hypothesized that the elderly would exhibit an impaired functional capacity at altitude, with increased myocardial ischemia compared with sea level (SL). Methods and Results Twenty veterans (68±3 years) were studied at (1) SL, (2) acute simulated altitude to 2500 m, and (3) after 5 days of acclimatization to 2500 m. With acute altitude, Pa o 2 and oxyhemoglobin saturation decreased and pulmonary artery pressure increased 43%, associated with sympathetic activation. V̇ o 2peak decreased 12% acutely but normalized after acclimatization. The best predictor of V̇ o 2peak with acute altitude was V̇ o 2peak at SL ( r =.94). The double product that induced 1-mm ST depression during exercise with acute altitude was 5% less than SL but normalized after acclimatization. One patient with severe coronary disease sustained a myocardial infarction after an exercise test. Conclusions Moderate altitude exposure in the elderly is associated with hypoxemia, sympathetic activation, and pulmonary hypertension resulting in a reduced exercise capacity that is predictable based on exercise performance at SL. Patients with coronary artery disease who are well compensated at SL do well at moderate altitude, although acutely ischemia may be provoked at modestly lower myocardial and systemic work rates. The elderly acclimatize well with normalization of SL performance after 5 days. A prudent policy would be for elderly individuals, particularly those with coronary artery disease, to limit their activity during the first few days at altitude to allow this acclimatization process to occur.
Physical Factors Which Influence Vascular Caliber and Blood Flow
Authors: LYSLE H. PETERSON
Journal: Circulation Research (1966)

1. The radii of blood vessels constitute their major biological functions. 2. The radii of blood vessels are abnormally reduced in most forms of hypertension. 3. The radii of blood vessels are determined by distending pressure and by the geometry and stiffness of the wall material. The latter two factors determine the vessel tone. Thus, tone is defined by those factors which determine vessel radius with respect to distending pressure. 4. It is now possible to measure simultaneously the distending pressure and the factors which determine tone, as well as the radius of vessels. Thus, it is possible to quantitate the factors which determine vascular tone: elastic stiffness (E), viscous stiffness (R), radius (r), and wall thickness (8). 5. These factors have been studied in intact dogs, and the tone of the major vessels of the vascular tree has been mapped out. 6. As the vessel wall itself becomes stiffened, compensatory changes may occur in the geometry. As the vessel dilates and thins, the r/8 ratio enlarges, and the vessel becomes relatively more distensible. 7. Little is known about the changes within the vessel wall which are associated with the mechanical properties of the wall, such as smooth muscle, connective tissue, water and electrolyte concentrations and distributions, the nonhomogenous aspects of the tissue components, or the extent of isovolumetric considerations that are applicable. 8. One of the most challenging aspects of cardiovascular research is to define appropriately and measure the factors mentioned above. They certainly represent part of the key to understanding the etiology and development of hypertension.
Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women
Authors: Madge R Vickers, Alastair H MacLennan, Beverley Lawton, Deborah Ford, Jeannett Martin, Sarah K Meredith, Bianca L DeStavola, Sally Rose, Anthony Dowell, Helen C Wilkes, Janet H Darbyshire, Tom W Meade
Journal: BMJ (2007)

<b>Objective</b> To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy). <b>Design</b> Multicentre, randomised, placebo controlled, double blind trial. <b>Setting</b> General practices in UK (384), Australia (91), and New Zealand (24). <b>Participants</b> Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56 583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22 300) started treatment. <b>Interventions</b> Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned. <b>Main outcome measures</b> Primary outcomes: major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life. <b>Results</b> The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women9s health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 <i>v</i> 0, P=0.016) and venous thromboembolisms (22 <i>v</i> 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 <i>v</i> 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 <i>v</i> 19, 0.73 (0.37 to 1.46)), fractures (40 <i>v</i> 58, 0.69 (0.46 to 1.03)), and overall deaths (8 <i>v</i> 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences. <b>Conclusions</b> Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause. The results are consistent with the findings of the women9s health initiative study and secondary prevention studies. Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause, when the effect may be different. <b>Trial registration</b> Current Controlled Trials ISRCTN 63718836
Neuroblastoma: Clinical Perspectives, Monoclonal Antibodies, and Retinoic Acid
Authors: ROBERT C. SEEGER
Journal: Annals of Internal Medicine (1982)

Neuroblastoma, the second commonest solid tumor in children, is a neoplasm of the peripheral autonomic nervous system that usually occurs before children are 6 years old. Therapy of localized tumor (clinical stage I and II) and of a special form of metastatic tumor (clinical stage IV-S) is usually successful, but treatment of widespread regional (clinical stage III) or metastatic (clinical stage IV) neuroblastoma is almost uniformly unsuccessful. Unfortunately, two thirds of children have stage III or IV disease at diagnosis. Several clinical trials are in progress. Preclinical investigations with monoclonal antibodies and retinoic acid may lead to new therapies. Monoclonal antibodies that react relatively selectively with neuroblastoma cells may be useful for diagnosis and therapy. Neuroblastoma cells have cytoplasmic retinoicacid-binding proteins; treatment of cultured cells with retinoic acid induces morphologic maturation and markedly inhibits proliferation.
Radionuclide Cerebral Angiographic Findings in Paget??s Disease of the Skull
Authors: EMILIO G. FLORES, KWANG G. JOO, GEORGE R. BAEUMLER
Journal: Clinical Nuclear Medicine (1982)

FLORES, EMILIO G. Jr. M.D.; JOO, KWANG G. M.D.; BAEUMLER, GEORGE R. M.D. Author Information
253 SIRNA TARGETING HEPATITIS B VIRUS X AND AZA-C INHIBIT GROWTH OF HEPATOCELLULAR CARCINOMA CELLS VIA INDUCTION OF G0/G1 ARREST DUE TO REVERSE P16 HYPERMETHYLATION
Authors: L. Yang, M. Wu, X. Wang, J. Kuang, J. Zhu, X. Yao, Q. Xie, Z. Gao, G. Chen
Journal: Journal of Hepatology (2009)
Molecular composition and pathology of entheses on the medial and lateral epicondyles of the humerus: a structural basis for epicondylitis
Authors: S Milz, T Tischer, A Buettner, M Schieker, M Maier, S Redman, P Emery, D McGonagle, M Benjamin
Journal: Annals of the Rheumatic Diseases (2004)

To improve the understanding of epicondylitis by describing the normal structure and composition of the entheses associated with the medial and lateral epicondyles and their histopathology in elderly cadavers.Medial and lateral epicondyles were obtained from 12 cadavers. Six middle aged cadavers (mean 47 years) were used to assess the molecular composition of "normal" entheses from people within an age range vulnerable to epicondylitis. Cryosections of epicondylar entheses were immunolabelled with monoclonal antibodies against molecules associated with fibrocartilage and related tissues. A further six elderly cadavers (mean 84 years) were used for histology to assess features of entheses related to increasing age.Tendon entheses on both epicondyles fused with those of the collateral ligaments and formed a more extensive structure than hitherto appreciated. Fibrocartilage (which labelled for type II collagen and aggrecan) was a constant feature of all entheses. Entheses from elderly subjects showed extensive microscopic damage, hitherto regarded as a hallmark of epicondylitis.Fibrocartilage is a normal feature and not always a sign of enthesopathy. Furthermore, pathological changes documented in patients with epicondylitis may also be seen in elderly people. The fusion of the common extensor and flexor tendon entheses with those of the collateral ligaments suggests that the latter may be implicated as well. This may explain why pain and tenderness in epicondylitis may extend locally beyond the tendon enthesis and why some patients are refractory to local treatments.
Tetanus Antitoxin; Its Preparation and Properties
Authors: R. T. Hewlett
Journal: BMJ (1895)

TETANUS ANTITOXIN.article on Tumours, in Pitha and Billroth's well-known Chirurgie, mentions that dermoids sometimes follow injury (trauma) in early life, and as an illustration writes:" A child, 6 years old, was seized in the right orbital region by a dog, but without actual wound of the skin; some weeks later a tumour appeared in this region, its presence -had never been noticed before.It gave the characters of a dermoid."Among my own cases I have an example of an implanta- tion cyst in the forehead of a pretty girl, which formed in the scar of a wound, due to a blow from an angular stone, three years previously.
Tea tree oil reduces histamine-induced skin inflammation
Authors: K.J. Koh, A.L. Pearce, G. Marshman, J.J. Finlay-Jones, P.H. Hart
Journal: British Journal of Dermatology (2002)

Tea tree oil is the essential oil steam-distilled from Melaleuca alternifolia, an Australian native plant. In recent years it has become increasingly popular as an antimicrobial for the treatment of conditions such as tinea pedis and acne.To investigate the anti-inflammatory properties of tea tree oil on histamine-induced weal and flare.Twenty-seven volunteers were injected intradermally in each forearm (study and control assigned on an alternating basis) with histamine diphosphate (5 microg in 50 microL). Flare and weal diameters and double skin thickness were measured every 10 min for 1 h to calculate flare area and weal volume. At 20 min, 25 microL of 100% tea tree oil was applied topically to the study forearm of 21 volunteers. For six volunteers, 25 microL paraffin oil was applied instead of tea tree oil.Application of liquid paraffin had no significant effect on histamine-induced weal and flare. There was also no difference in mean flare area between control arms and those on which tea tree oil was applied. However, mean weal volume significantly decreased after tea tree oil application (10 min after tea tree oil application, P = 0.0004, Mann-Whitney U-test).This is the first study to show experimentally that tea tree oil can reduce histamine-induced skin inflammation.
Journal accused of manipulating impact factor
Authors: R. Smith
Journal: BMJ (1997)

The journal Leukemia , which is owned by Macmillan magazines, has been accused of trying to manipulate its impact factor, the measure used to rank the importance of scientific journals. The accusation comes from Terry Hamblin, consultant haematologist at the Royal Bournemouth Hospital and editor of Leukemia Research , a rival to Leukemia .

Dr Hamblin has sent the BMJ a copy of a letter received by authors who had submitted a paper to Leukemia in October 1996 asking them to increase the number of references to papers published in Leukemia . This would increase the journal's impact factor, which is calculated by dividing the number of …
BI-12 * RTOG 0525 RECURSIVE PARTITIONING ANALYSIS BASED ON CLINICAL AND PROTEIN BIOMARKER PARAMETERS
Authors: E. H. Bell, S. Pugh, M. Gilbert, M. Mehta, A. Klimowicz, A. Magliocco, M. Bredel, P. Robe, A. Grosu, R. Stupp, W. Curran, B. Corn, P. Brown, J. Glass, L. Souhami, R. Jeffrey Lee, D. Brachman, M. Deutsch, M. Won, A. Chakravarti
Journal: Neuro-Oncology (2014)

BACKGROUND: The objective was to revise the clinically-based RTOG RPA (cRPA) model for glioblastoma (GBM) through incorporation of protein biomarkers. METHODS: RTOG 0525 patients with adequate specimens were analyzed for up to 22 protein biomarkers representing key pathways putatively associated with treatment resistance and/or adverse clinical outcome. Protein expression levels were quantified using a molecular microscopy-based approach (AQUA) and cytoplasmic versus nuclear expression was determined. Each protein biomarker was analyzed for prognostic significance by uni- and multivariate (UVA, MVA) Cox regression analysis. Proteins significantly associated with survival along with age, KPS, neurologic function, and surgery status were incorporated into the clinical RPA model (cpRPA). RESULTS: 428 samples were analyzed. On stepwise MVA (n = 164), nuclear MGMT (p = 0.001, HR = 1.84), and cMET (p = 0.001, HR = 1.83) were independently prognostic. The new cpRPA model was developed using 168 patients with all significant protein biomarker data and was comprised of three classes incorporating nuclear MGMT, age, and performance status. The new cpRPA model showed greater separation of prognostic classes of GBM relative to the currently used cRPA model (Median overall-survival for Classes III, IV, and V are 30.0, 16.1, and 11.4 months for cRPA and 21.1, 11.3, and 4.8 months for the cpRPA based on three new cpRPA classes (I-III) (p < 0.001). CONCLUSIONS: Incorporating protein biomarkers with variables in the existing cRPA produces greater separation of the survival curves, suggesting a role for further validation studies. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, U10 CA37422, U24CA180803, RO1CA108633 (To AC), 1RC2CA148190 (To AC) U10CA180850-01 (To AC), 1R01CA169368 (To AC) from the National Cancer Institute (NCI), Brain Tumor Funders Collaborative Grant (To AC), Ohio State University Comprehensive Cancer Center Award (To AC) and Merck & Co.
COST EFFECTIVENESS OF FDG WHOLE BODY PET IN THE EVALUATION OF RENAL CELL CA
Authors: C. K. Hoh, R. A. Figlin, A. Belldegrun, S. J Lee, M. E. Phelps, J. Maddahi
Journal: Clinical Nuclear Medicine (1995)

Hoh, C. K.; Figlin, R. A.; Belldegrun, A.; Lee, S. J; Phelps, M. E.; Maddahi, J. Author Information
The Mortal Presidency: Illness and Anguish in the White House
Authors: William K. Beatty
Journal: JAMA (1993)

Gilbert, a professor of political science, examines the effects of physical and psychological illnesses on Calvin Coolidge, Franklin Roosevelt, Dwight Eisenhower, John Kennedy, and Ronald Reagan. The sections on Coolidge, Eisenhower, and Reagan are the most interesting, since FDR and JFK have been much more thoroughly worked over in the literature. Coolidge, despite the general view that he was a lackadaisical and weak president, did well in his first year after Harding's death on August 2,1923. Gilbert shows that Coolidge put in full and active days in his office. He worked well with Congress and achieved much improved relations with Mexico. However, shortly after the Republicans nominated Coolidge for the presidency in June 1924, 16-year-old Calvin Junior acquired a blister on his foot that became infected and died a week later. President Coolidge never completely recovered. Beginning with the fact that Coolidge did not pay the undertaker's bill for three
Palliative Treatment of Carcinoma of the Rectum by Endoscopic Injection of Polidocanol
Authors: E. Marini, F. Frigo, L. Cavarzere, S. Cutolo, L. Palazzin, F. Orcalli
Journal: Endoscopy (1990)

Between January 1987 and December 1988, at the Surgical Department of Chiarenzi Hospital, five patients underwent endoscopic intratumoral injection of polidocanol for palliative treatment of inoperable carcinoma of the rectum. Histological evaluation was performed in all cases. The patients comprised two males and three females aged 78 to 88 years (mean 83.4). One of them refused surgery for recurrent rectal cancer, four consulted us with impending intestinal obstruction; three were inoperable due to local spread of the tumor and poor general condition, the other was in a poor general condition due to massive metastatic hepatic disease. In all the patients, we observed remission of the obstructive symptoms with no major complications; none of them has required a colostomy. The follow-up period has covered a period of two months to two years. The technique of injection is simple, inexpensive and, properly performed, safe. All these advantages make this type of palliative treatment for rectal cancer interesting, even when compared with laser treatment, urological resectoscope or electric snare resection, and electrocoagulation.
Abstract 3194: Platycodin D induces growth arrest and cell cycle arrest by activating MDM2 and interacting with FOXO3a in prostate cancer
Authors: Hongxia Xu, Rui Zhou, Zongliang Lu, Kai Liu
Journal: Cancer Research (2014)

Abstract Purpose: The present study was designed to evaluate the anti-tumor activity and possible mechanism of action of Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, in human prostate cancer. Experimental Design: Human prostate cancer cells with different p53 status (p53 wildtype LNCaP cells, p53 null PC3 cells and p53 mutant DU145 cells), and the normal human prostate cell line, RWPE-1, were exposed to various concentrations of PD to compare its cytotoxicity in vitro (via the MTT assay). Detailed invitro and invivo studies on the anti-tumor effects of PD were then performed. Results: PD exerted cytotoxicity against all three prostate cancer cell lines, with half-maximal inhibitory concentrations in the range of 11.16 to 26.13μmol/L. The PC3 cells were the most sensitive to PD, whereas RWPE-1 cells were not sensitive to PD.A further study in these cell lines showed that PD could potently affect the cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (by Annexin V-FITC flow cytometry) and cause cell cycle arrest (PI staining). After being treated with PD for 48 hours,the DU145 and LNCaP cells were arrested in the G0 /G1 phase, and the PC3 cells were arrested in the G2/M phase. A Western blot analysis indicated that PD decreased the expression of MDM2 and increased the expression levels of FOXO3a, p21 and p27 in the three cell lines. In PC3 cells, PD exposure decreased the levels of cell cycle-related proteins, including E2F1, cdk2, cdk4, cdk6, cyclin D1 and cdc2. PD exposure increased apoptosis-related proteins, Bax, caspase9 and caspase3, and downregulated Bcl-2, PARP, and caspase8. Real-time PCR indicated that the same changes had occurred at the transcriptional level for all of these targets. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blot analysis of the xenograft tumors indicated that similar changes in protein expression also occurred in vivo. Conclusion: PD exhibits significant activity against prostate cancer cells in a p53-independent manner. MDM2 and the FOXO3a transcription factor appear to be involved in the mechanism of action of PD, which provides a basis for future development of this agent for human prostate cancer therapy. Citation Format: Hongxia Xu, Rui Zhou, Zongliang Lu, Kai Liu. Platycodin D induces growth arrest and cell cycle arrest by activating MDM2 and interacting with FOXO3a in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3194. doi:10.1158/1538-7445.AM2014-3194
Guy's Hospital Has Seen Changes in 163 Years, Now Initiates 'Model Management' of Its Own
Authors: John F. Henahan
Journal: JAMA (1989)

ON FEBRUARY 1, the Conservative Thatcher government in Great Britain proposed a series of major changes in the country's National Health Service that are more drastic and far-reaching than anything that has occurred since "socialized medicine" was introduced by the then Labour government 40 years ago. The changes (detailed in the accompanying article) will have a major impact on how medicine will be practiced in the United Kingdom in the future and will inevitably influence how physicians will treat their patients and the extent to which patients will be able to get good medical care. (Activation of the new plan awaits approval by the British Parliament, but considering that Prime Minister Margaret Thatcher's Conservative party has a majority of about 100, it will almost certainly be voted into law. However, even if that happened immediately, it is estimated that it would take about 3 years before it was fully implemented.)