tbuckley/cabot-search huggingface dataset:
Abstract 4458: Antiproliferative effects of γ-tocotrienol are mediated by suppression in the activation of Met tyrosine kinase receptors in neoplastic +SA mammary epithelial cells
Authors: Sunitha V. Bachawal, Vikram B. Wali, Paul W. Sylvester
Journal: Cancer Research (2010)

Abstract γ-Tocotrienol, a member of vitamin E family of compounds, displays potent anticancer activity against breast and other types of cancers. Previous studies have shown that the antiproliferative effects of γ-tocotrienol are associated with the suppression in the epidermal growth factor (EGF)-dependent phosphatidylinositol-3-kinase (PI3K)-dependent kinase-1 (PDK-1) and Akt phosphorylation in neoplastic +SA mammary epithelial cells. Also, studies showed that γ-tocotrienol treatment had no direct effect on Akt activity and did not alter the relative intracellular levels of PI3K, indicating that γ-tocotrienol might act upstream of the PI3K/PDK-1/Akt pathways at the level of membrane tyrosine kinase receptors in +SA mammary tumor cells. Since aberrant activation of the Met tyrosine kinase receptors is observed in various types of cancers and is associated with poor prognosis, studies were conducted to determine the effect of γ-tocotrienol on EGF and hepatocyte growth factor (HGF)-dependent activation of Met tyrosine kinase receptors in +SA mammary tumor cells. Treatment with serum-free media containing various doses of EGF (1-10 ng/ml) or HGF (1-10 ng/ml) significantly increased the growth of +SA mammary tumor cells as compared to serum-free control group over a 3-day culture period. Stimulation of +SA cells with EGF (10 ng/ml) or HGF (10 ng/ml) resulted in the activation of Met tyrosine kinase receptors. Treatment with Met tyrosine kinase inhibitor, SU11274 (5.5 μM) or γ-tocotrienol (4 μM) inhibited the EGF or HGF-dependent growth and activation of Met receptors in +SA mammary tumor cells after a 3-day culture period. Also, knockdown of Met receptors using Met specific siRNA decreased the expression of Met receptors and significantly inhibited the EGF or HGF-dependent growth of +SA cells. Additional studies showed that when +SA cells were simultaneously exposed to EGF (10 ng/ml) and HGF (10 ng/ml), the growth inhibitory effects of γ-tocotrienol (4 μM) and SU11274 (5.5 μM) were significantly reversed, associated with the activation of Met receptors. However, combined treatment with low doses of γ-tocotrienol (2 μM) and SU11274 (3 μM) inhibited the EGF and/or HGF-dependent growth of neoplastic +SA mammary epithelial cells. These results strongly suggest that γ-tocotrienol treatment may provide significant health benefit in the prevention and/or treatment of breast cancer in women with deregulated HGF/Met signaling. Supported by grants from NIH (CA86833) and First Tech International Ltd. 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 4458.
Puncture of Solid Pancreatic Tumors Guided by Endoscopic Ultrasonography: A Pilot Study Series Comparing Trucut and 19-Gauge and 22-Gauge Aspiration Needles
Authors: T. Itoi, F. Itokawa, A. Sofuni, K. Nakamura, A. Tsuchida, K. Yamao, T. Kawai, F. Moriyasu
Journal: Endoscopy (2005)

Background and Study Aims: The aim of this prospective study was to compare endoscopic ultrasonography-guided Trucut needle biopsy (EUS-TNB) with EUS-guided fine-needle aspiration biopsy (EUS-FNAB) using 19- and 22-gauge needles for biopsy from different sites in patients with solid pancreatic cancers. Patients and Methods: Sixteen consecutive patients with masses in the uncinate process (n = 3), the head (n = 5), or the body and tail (n = 8) of the pancreas underwent both EUS-TNB and EUS-FNAB. The specimens obtained were evaluated by histopathological analysis alone Results: Tissue specimens were obtained by Trucut needle, and by 19-gauge and 22-gauge aspiration needles in 69 %, 69 %, and 100 % of patients respectively. Sensitivity for malignancy was 69 % for all needles. Tissue sampling by Trucut and by 19-gauge aspiration needle from masses in the uncinate process was impossible. The sensitivity of the Trucut and 19-gauge aspiration needles was 100 % in the 11 patients with successful procedures. If Trucut or19-gauge aspiration needles had been used for body and tail masses, and the 22-gauge aspiration needle for masses in the uncinate process and head, the sensitivity for malignancy would have been 81 %. Conclusions: EUS-TNB allows reliable tissue sampling for the diagnosis of pancreatic masses, but its use is limited to lesions in the body and tail of the pancreas. EUS-FNAB using a 22-gauge needle may be useful for accurate diagnosis in some patients with masses in the uncinate process or the head of the pancreas.
The Cost of Medicine
Authors: Shyam K. Bhat
Journal: Annals of Internal Medicine (2003)

On Being a Doctor1 July 2003The Cost of MedicineShyam K. Bhat, MDShyam K. Bhat, MDFrom the Southern Illnois University School of Medicine, Springfield, IL 62794.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-1-200307010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It is obvious that the patient is dying. She is 92 years old with multiple medical problemsso many that my tired intern mind can barely list them on morning rounds. History of metastatic colon cancer, diabetes, advanced dementia, congestive heart failure But the family wants everything doneso we do our job efficiently and thoroughly. The attending physician recommends an MRI to clarify the diagnosis of the patient's sudden limb weakness, and I write the order down, then initial it. It feels routine now, this mundane ordering of expensive tests with no questions asked about cost. No more do I feel ... Author, Article, and Disclosure InformationAffiliations: From the Southern Illnois University School of Medicine, Springfield, IL 62794.Corresponding Author: Shyam K. Bhat, MD, Southern Illinois University School of Medicine, PO Box 19642, Springfield, IL 62794-9642; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Cost of Medicine Barry Kisloff Metrics Cited byEvidence-Based Medicine, Quality of Life, and the Cost of MedicineThe Cost of MedicineBarry Kisloff, MD 1 July 2003Volume 139, Issue 1Page: 74-75KeywordsChildrenEmotionsFoodInsulinSaltsShouldersSleepSmellThoraxVomiting ePublished: 1 July 2003 Issue Published: 1 July 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cardiology: the development of a managed clinical network
Authors: C D Baker
Journal: BMJ (2000)

Based on a presentation from the Millennium Festival of Medicine The idea that a single hospital can provide all the facilities necessary for its catchment area is no longer tenable. In 1998 the Scottish acute services review recognised this and proposed the development of managed clinical networks as an innovative way of providing acute services in the NHS in Scotland.1 We describe here the characteristics of these networks. Managed clinical networks are linked groups of health professionals and organisations from primary, secondary, and tertiary care, working in a coordinated manner that is not constrained by existing organisational or professional boundaries to ensure equitable provision of high quality, clinically effective care. Networks can be of several types—for example, they can cover a specific disease, such as peripheral vascular disease; a specific specialty, such as neurology; or a specific function, such as medical receiving. The term network might suggest diffused responsibility, but these networks are not casual or informal: the point is that they are managed. The core principles of a managed clinical network were set out by the Scottish Office department of health management executive in 1999.2 They include:
Statistically designed experiments to screen chemical mixtures for possible interactions.
Authors: J P Groten, O Tajima, V J Feron, E D Schoen
Journal: Environmental Health Perspectives (1998)

For the accurate analysis of possible interactive effects of chemicals in a defined mixture, statistical designs are necessary to develop clear and manageable experiments. For instance, factorial designs have been successfully used to detect two-factor interactions. Particularly useful for this purpose are fractionated factorial designs, requiring only a fraction of all possible combinations of a full factorial design. Once the potential interaction has been detected with a fractionated design, a more accurate analysis can be performed for the particular binary mixtures to ensure and characterize these interactions. In this paper this approach is illustrated using an in vitro cytotoxicity assay to detect the presence of mixtures of Fusarium mycotoxins in contaminated food samples. We have investigated interactions between five mycotoxin species (Trichothecenes, Fumonisins, and Zearalenone) using the DNA synthesis inhibition assay in L929 fibroblasts. First, a central composite design was applied to identify possible interactive effects between mycotoxins in the mixtures (27 combinations from 5(5) possible combinations). Then two-factor interactions of particular interest were further analyzed by the use of a full factorial design (5 x 5 design) to characterize the nature of those interactions more precisely. Results show that combined exposure to several classes of mycotoxins generally results in effect addition with a few minor exceptions indicating synergistic interactions. In general, the nature of the interactions characterized in the full factorial design was similar to the nature of those observed in the central composite design. However, the magnitude of interaction was relatively small in the full factorial design.
BASELINE RENAL DYSFUNCTION AND ACUTE KIDNEY INJURY ARE ASSOCIATED WITH DECREASED RATES OF ANGIOTENSIN CONVERTING ENZYME AND ANGIOTENSIN RECEPTOR BLOCKER PRESCRIPTION AT DISCHARGE FOLLOWING HOSPITALIZATION FOR ACUTE MYOCARDIAL INFARCTION
Authors: Abhinav Sharma, James Wetmore, Fengming Tang, Philip Jones, John Spertus
Journal: Journal of the American College of Cardiology (2014)
The Evolving Technology of Venous Access
Authors: Richard P. Wenzel, Michael B. Edmond
Journal: New England Journal of Medicine (1999)

Imagine the era — only a century ago — when no means of vascular access existed for the life-sustaining support of critically ill patients. In 1832, in the wake of the second cholera pandemic, there were encouraging reports that silver cannulas attached to syringes could be introduced into basilic veins for rehydration.1 Because of the limited success with this technique, intravenous saline would not be accepted as therapy for many decades. With advancing knowledge of electrolyte physiology and the availability of steel needles, however, the therapeutic use of intravenous fluid became established.Subsequently, the advent of penicillin and the need . . .
Antidepressant Use in Patients Prescribed β-Blockers
Authors: David J. Graham
Journal: JAMA (1986)

<h3>To the Editor.—</h3> We read with interest the article by Avorn et al<sup>1</sup>showing an increased prevalence of tricyclic antidepressant (TCA) use among patients ever receiving β-blockers, compared with selected antihypertensive and antidiabetic drugs. This may be consistent with the labeling as shown in the<i>Physician's Desk Reference</i>, which lists depression as a possible side effect of β-blockers use. Our experience with the Medicaid data base used in this study leads us to raise three concerns about the methodology employed, as they represent potential sources of bias in the study that collectively may serve either to underestimate a real association or generate a spurious one. 1. The study design used does not distinguish which came first, the "exposure" (eg, β-blockers or hydralazine use) or the "outcome" of interest (TCA use), and hence does not examine directly the underlying question of temporal relationship between the two. Although we do not
Comparison of Different Metronidazole Therapeutic Regimens for Bacterial Vaginosis
Authors: Victor I. Lugo-Miro, Mitra Green, Lynnette Mazur
Journal: JAMA (1992)

<h3>Objective.</h3> —To evaluate the treatment of bacterial vaginosis with metronidazole to determine if there is a therapeutic regimen that is superior to all others with regard to cure and recurrence rates. <h3>Data Sources.</h3> —Computer-assisted literature search, Medical Subject Index review, and references cited in articles identified. <h3>Study Selection.</h3> —Clinical trials comparing different oral metronidazole regimens in which diagnostic criteria for bacterial vaginosis and criteria to detect cure to treatment were described. <h3>Data Extraction.</h3> —Articles that met inclusion criteria were critically appraised and those that passed were included in the analysis. Of 52 initial articles, 10 met criteria for inclusion and passed critical appraisal. <h3>Data Synthesis.</h3> —Patients were divided in groups according to the duration of therapy received: group A (n=413), 2-g single dose; group B (n=193), 2-g single daily dose for 2 days; group C (n=317), 5 days; and group D (n=280), 7 days. Cure rates on initial evaluation for the groups were 85%, 87%, 86%, and 87%, respectively. χ<sup>2</sup>Contingency table analysis showed no significant difference in cure rates among the groups (<i>P</i>=.78). Only 465 of these patients were evaluated for recurrence of disease. There was no significant difference in cure rates after 4 weeks of therapy (<i>P</i>=.4). <h3>Conclusions.</h3> —A 2-g single-dose metronidazole regimen is as effective as a single daily dose given for 2 days or a 5-day course or a 7-day course. (<i>JAMA</i>. 1992;268:92-95)
The computational nature of associative learning
Authors: N. A. Schmajuk, G. M. Kutlu
Journal: Behavioral and Brain Sciences (2009)

Abstract An attentional-associative model (Schmajuk et al. 1996), previously evaluated against multiple sets of classical conditioning data, is applied to causal learning. In agreement with Mitchell et al.'s suggestion, according to the model associative learning can be a conscious, controlled process. However, whereas our model correctly predicts blocking following or preceding subadditive training, the propositional approach cannot account for those results.
ISOLATION OF HTLV-I FROM CEREBROSPINAL FLUID OF A PATIENT WITH MYELOPATHY
Authors: Shozo Hirose, Yoshiki Uemura, Masatoshi Fujishita, Takao Kitagawa, Makoto Yamashita, Jun Imamura, Yuji Ohtsuki, Hirokini Taguchi, Isao Miyoshi
Journal: The Lancet (1986)
Treatment for Cervical Intraepithelial Neoplasia and Risk of Preterm Delivery
Authors: Lynn Sadler
Journal: JAMA (2004)

ContextIt is unclear whether treatments for cervical intraepithelial neoplasia (CIN) increase the subsequent risk of preterm delivery. Most studies have lacked sufficient sample size, mixed heterogeneous subtypes of preterm delivery, and failed to control for confounding factors.ObjectiveTo determine whether cervical laser and loop electrosurgical excision procedure (LEEP) treatments increase risk of preterm delivery and its subtypes.Design, Setting, and ParticipantsRetrospective cohort study conducted among women evaluated at a colposcopy clinic serving Auckland, New Zealand (1988-2000), comparing delivery outcomes of untreated women (n = 426) and those treated (n = 652) with laser conization, laser ablation, or LEEP. Record linkage using unique health identifiers identified women who had subsequent deliveries.Main Outcome MeasuresTotal preterm delivery and its subtypes, spontaneous labor and premature rupture of membranes before 37 weeks' gestation (pPROM).ResultsThe overall rate of preterm delivery was 13.8%. The rate of pPROM was 6.2% and the rate of spontaneous preterm delivery was 3.8%. Analyses showed no significant increase in risk of total preterm delivery (adjusted relative risk [aRR], 1.1; 95% confidence interval [CI], 0.8-1.5) or spontaneous preterm delivery (aRR, 1.3; 95% CI, 0.7-2.6) for any treatment. Risk of pPROM was significantly increased following treatment with laser conization (aRR, 2.7; 95% CI, 1.3-5.6) or LEEP (aRR, 1.9; 95% CI, 1.0-3.8), but not laser ablation (aRR, 1.1; 95% CI, 0.5-2.4). Moreover, risk of pPROM and total preterm delivery increased significantly with increasing height of tissue removed from the cervix in conization. Women in the highest tertile of cone height (≥1.7 cm) had a greater than 3-fold increase in risk of pPROM compared with untreated women (aRR, 3.6; 95% CI, 1.8-7.5).ConclusionsLEEP and laser cone treatments were associated with significantly increased risk of pPROM. Careful consideration should be given to treatment of CIN in women of reproductive age, especially when treatment might reasonably be delayed or targeted to high-risk cases.
Increased gastric juice epidermal growth factor after non-steroidal anti-inflammatory drug ingestion.
Authors: S M Kelly, J R Jenner, R J Dickinson, J O Hunter
Journal: Gut (1994)

Epidermal growth factor (EGF), present in saliva and gastric juice, is a potent mitogen and an important element of mucosal defence. Changes in salivary and gastric juice epidermal growth factor in response to non-steroidal anti-inflammatory drug (NSAIDs) ingestion were measured to assess the role of EGF in gastric mucosal adaptation to NSAIDs. Patients with arthritis underwent endoscopy with collection of saliva and gastric juice for EGF measurement, before and two weeks after continuous NSAID ingestion. During this period patients also received either the prostaglandin analogue misoprostol or placebo in addition to their NSAID. In the misoprostol group (n = 5) there was no observed mucosal damage and no change in either salivary or gastric juice EGF. In the placebo group (n = 10) three patients developed erosions. Salivary EGF did not change (mean (SEM) 3.02 (0.54) ng/ml v 2.80 (0.41) ng/ml) but gastric juice EGF increased from 0.42 (0.12) ng/ml to 0.69 (0.14) ng/ml (p &lt; 0.05). This increased EGF could contribute to the increased cellular proliferation observed during NSAID ingestion and may represent an important mechanism underlying gastric mucosal adaptation.
KATP -- fact or artefact? New thoughts on the mode of action of the potassium channel openers
Authors: G. Edwards, A. H Weston
Journal: Cardiovascular Research (1994)

Journal Article KATP — fact or artefact? New thoughts on the mode of action of the potassium channel openers Get access Gillian Edwards, Gillian Edwards Smooth Muscle Pharmacology Group, School of Biological Sciences, G38 Stopford Building, University of Manchester MI3 9PT, United Kingdom: G Edwards, A H Weston. Correspondence to Dr Edwards. Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur H Weston Arthur H Weston Smooth Muscle Pharmacology Group, School of Biological Sciences, G38 Stopford Building, University of Manchester MI3 9PT, United Kingdom: G Edwards, A H Weston. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 6, June 1994, Pages 735–737, https://doi.org/10.1093/cvr/28.6.735 Published: 01 June 1994 Article history Received: 20 January 1994 Published: 01 June 1994
Psychopharmacology: An Introduction to Experimental and Clinical Principles
Authors: Frank J. Ayd
Journal: JAMA (1973)

To attempt a comprehensive but concise review of the neuroanatomical, neurochemical, neurotransmitter, and neuropharmacological foundations of psychopharmacology (in animal and man), as well as all the available psychotropic drugs (sedatives, major and minor tranquilizers, anti-depressants, and psychostimulants, including the psychotomimetics) is a monumental task. Yet, the author has attempted this in less than 200 pages of text. The result mirrors his extensive review of the literature on psychopharmacology (the bibliography attests to this), his expertise in animal neuropsychopharmacology, and his interpretations as a nonclinician of the clinical and undesirable effects of psychotropics. The first five chapters, despite their terseness, are excellent overviews of the brain, the neuron, brain neurotransmitters, animal and human experimental methods in psychopharmacology, and the neurochemical correlates of behavior. The next six chapters are devoted to the psychotropics, beginning with a classification of these compounds and followed by a review of the general aspects, behavioral, clinical, and
Discrepancy between portal pressure and systemic hemodynamic changes after incremental doses of propranolol in a wake portal hypertensive rats
Authors: Abraham Koshy, Catherine Girod, Samuel S. Lee, Antoine Hadengue, Raimondo Cerini, Didier Lebrec
Journal: Hepatology (1989)

The effects of increasing doses of propranolol were studied in awake portal hypertensive rats in order to elucidate the relative effects of the β-blocker on systemic and splanchnic circulation. Hemodynamic responses to 0.1, 0.2 and 0.4 mg per min infusions of propranolol were compared with placebo in awake rats with portal hypertension due to portal vein stenosis. Heart rate significantly and progressively decreased from 356 ± 13 to 293 ± 10 beats per min (mean ± S.E.). Cardiac output significantly decreased from 54 ± 3 to 42 ± 3 ml per min per 100 gm body weight at the highest dose. Significant decrease in portal tributary blood flow from 27 ± 1 to 18 ± 1 ml per min, at 0.4 mg per min dose, was due not only to the decrease in cardiac output but also to a significant increase in portal tributary vascular resistance from 269 ± 17 to 368 ± 31 dyne per sec per cm5 × 103. However, portal pressure showed only an insignificant decrease from 14.9 ± 1.1 to 14.1 ± 1.4 mmHg. The reduction in portal pressure being minimal, in spite of a significant decrease in portal tributary blood flow, is explained by an increase in combined hepatic and collateral resistance from 44 ± 2 to 66 ± 4 dyne per sec per cm5 × 103, p<0.05, at 0.4 mg per min dose. We conclude that the systemic and splanchnic effects of propranolol show discrepancy at two levels. First, portal tributary blood flow is reduced more than expected by the decrease in cardiac output because of an increase in portal tributary vascular resistance. Second, despite the marked decrease in portal tributary blood flow, the reduction in portal pressure is minimal because of an increase in combined hepatic and collateral vascular resistance. We suggest, furthermore, that the discrepancy at these two levels may be more or less apparent depending on the dose of propranolol utilized.
WHO values health directly
Authors: P. Kowal, S. Chatterji
Journal: BMJ (2009)

The World Health Organization has a pathway to measure and value health.1

From 2002 to 2004 it asked over 300 000 people across 70 countries to value different health states using a visual analogue scale, supplementing this with studies comparing direct and indirect valuation methods.2 3 Using this information and guided by burden …