tbuckley/cabot-search huggingface dataset:
Abstract PL02: Adjuvant bisphosphonate therapy in breast cancer
Authors: M Gnant
Journal: Cancer Research (2013)

Abstract Breast cancer patients face challenges to skeletal integrity, both by caused by the disease but also as a side effect of standard endocrine therapy. Bisphosphonates inhibit osteoclast-mediated bone resorption, are approved as standard therapy for treating malignant bone disease from advanced cancers, and have shown efficacy for preventing cancer treatment-induced bone loss. Bisphosphonates also have demonstrated anti-cancer activity preclinically and in clinical trials during adjuvant breast cancer therapy. The metastasis-preventing effect of bisphosphonates has been explained by their putative effects on the bone marrow microenvironment, which provides a site for cancer cells to evade immune surveillance and adjuvant systemic anti-cancer therapy. Dormant tumor micrometastases are believed to be the ultimate source of disease persistence and relapse, and it has been suggested that adjuvant bisphosphonate treatment renders the bone marrow microenvironment less conducive to cancer (stem) cell survival. This plenary lecture will provide a brief overview of the numerous preclinical and early clinical studies of bisphosphonates demonstrating a variety of direct and indirect anticancer activities, including the „seed-and-soil” hypothesis, and the proven effects of bisphosphonates on disseminated tumor cells. However, key questions remain surrounding the role of adjuvant bisphosphonates in breast cancer, including selecting patient populations actually deriving benefit and optimal timing/scheduling of therapy. Despite thousands of patients have been included in randomized clinical trials of adjuvant bisphosphonates, significant controversy persists about the usefulness of this therapeutic approach: current clinical data show clear-cut improvements in disease outcomes with bisphosphonates in many studies, although not in all patient subsets: Strongest support for the potential adjuvant anticancer benefits from bisphosphonates has been demonstrated in women with established menopause (i.e., very low circulating estrogen levels). Also, initiating bisphosphonates early and concomitantly with adjuvant therapy generally provided the greatest benefits. In addition to earlier trials using oral bisphosphonates such as clodronate, recent clinical data from large phase 3 trials (e.g. ABCSG-12, ZO-FAST, and AZURE) demonstrate significantly improved disease-free survival with zoledronic acid in some patient populations with early breast cancer. Other bone-targeted treatment approaches such as denosumab are currently evaluated for adjuvant therapy in large clinical trials. This plenary lecture will review the available data and concepts with the ultimate aim of aiding physicians in providing bone-targeted therapy as part of their optimal breast cancer patient counseling and management. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PL02.
Testing Pancreatic Function
Authors: Frank P. Brooks
Journal: New England Journal of Medicine (1972)

FEW laboratory procedures are as accurate as would be desirable, but with pancreatic-function tests, the problem is compounded by the lack of criteria with which to establish an independently arrived at diagnosis. All too often one must depend upon the surgeon's interpretation of the consistence of the pancreas. A number of tests of pancreatic function have value when interpreted in conjunction with the clinical situation.Table 1 shows the tests, classified according to the material used in the procedures. In general the blood and urine tests are more useful in acute pancreatic disease, whereas the analysis of duodenal content and stool is . . .
Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxins
Authors: Jayashree Aiyar, Jane M. Withka, James P. Rizzi, David H. Singleton, Glenn C. Andrews, Wen Lin, James Boyd, Douglas C. Hanson, Mariella Simon, Brent Dethlefs, Chao-lin Lee, James E. Hall, George A. Gutman, K. George Chandy
Journal: Neuron (1995)
A Prognostic System for Transient Ischemia or Minor Stroke
Authors: Walter N. Kernan, Ralph I. Horwitz, Lawrence M. Brass, Catherine M. Viscoli, Kenneth J. W. Taylor
Journal: Annals of Internal Medicine (1991)

To build a prognostic system for patients with carotid transient ischemic attack or minor stroke.Inception cohort study with 2-year follow-up.Urban community teaching hospital.Eligible patients (n = 142), identified on a carotid ultrasound roster, had been hospitalized between 1984 and 1987 within 30 days of a first carotid transient ischemic attack or minor stroke.Stroke or death within 2 years.Three factors were associated with stroke or death: age of more than 65 years, diabetes, and hypertension. Based on regression coefficients, age of more than 65 years was assigned 3 points; diabetes, 3 points; and hypertension, 2 points. An initial prognostic system comprised risk groups 1 (0 points), 2 (1 to 5 points), and 3 (6 to 8 points). Outcome rates in the three groups were 2%, 31%, and 54% (P less than 0.0001), respectively. In an independent test sample, the corresponding outcome rates for the initial system were 12%, 21%, and 31% (P = 0.04). A final prognostic system, including two additional predictors (coronary heart disease [1 point] and the distinction between stroke and transient ischemic attack for the baseline event [2 points]), comprised risk groups 1 (0 to 2 points), 2 (3 to 6 points), and 3 (7 to 11 points). Corresponding outcome rates were 3%, 27%, and 48% (P less than 0.001) in the original cohort and 10%, 21%, and 59% (P less than 0.001) in the test cohort.For selected patients with carotid transient ischemia or minor stroke, five clinical features can be combined to stratify effectively the risk for a subsequent stroke or death.
Symptomatic Hiatal Hernia
Authors: R. W. Postlethwait
Journal: JAMA (1961)

<h3>To the Editor:—</h3> InThe Journalof July 29 (<b>177:</b>282, 1961) a question concerned therapy for symptomatic hiatal hernia. Dr. R. E. Braucher concisely described difficulties in diagnosis and outlined nonoperative treatment. His statements, "Only rarely should operation be necessary" and "Surgical treatment should be reserved for complications which cannot be treated medically, such as perforation or strangulation," are, in my opinion, incorrect Paraesophageal hernia may be complicated by perforation or strangulation; sliding hiatal hernia is rarely. The sliding hernia is much more common by a ratio of about 20 to 1. Sliding hiatal hernia is protean in its manifestations and complications. Reflux esophagitis and not the size of the hernia is the most frequent basis for the difficulties, and this is usually corrected by operation. One of the most serious complications is a rigid stricture with shortening of the esophagus which presents a most difficult problem in treatment.
Platelet thrombus formation on collagen type I. A model of deep vessel injury. Influence of blood rheology, von Willebrand factor, and blood coagulation.
Authors: L Badimon, J J Badimon, V T Turitto, S Vallabhajosula, V Fuster
Journal: Circulation (1988)

Collagen type I is a major component of atherosclerotic vessel wall that is exposed on deep vessel injury, such as in balloon angioplasty or plaque rupture. Collagen type I from pig Achilles tendon was mounted in a tubular perfusion chamber placed within an extracorporeal circuit (carotid artery to jugular vein). The material was exposed to blood from normal pigs (n = 13), severe homozygous von Willebrand factor (vWF)-deficient pigs (vWF less than 3%) (n = 6), and heterozygous vWF-deficient pigs (vWF = 24%) (n = 2). Thrombus formation was measured by autologous 111In-platelet labeling and by ultrastructural morphology. Heparinized and native blood from these pigs was perfused over the substrate for 3 and 5 minutes at local shear rates from 212 to 3,380/sec. On collagen type I exposed to nonanticoagulated blood, for all exposure times studied, thrombus formation in the absence of vWF was significantly reduced at high shear rate typical of stenotic areas but not at low shear rate typical of unobstructed medium-size arteries. A similar inhibition in thrombus formation due to vWF deficiency was observed in both heparinized and native blood; however, thrombus formation was significantly more reduced (p less than 0.05) in the presence of heparin, presumably due to the lack of stability of the accumulated platelets in the absence of fibrin formation. Intermediate levels of vWF, as in heterozygous von Willebrand's disease (vWD), support platelet deposition to extents not significantly different from normal conditions. Therefore, on collagen type I, both the activation of blood coagulation proteins and the presence of vWF contribute significantly to the platelet-platelet interactions necessary for thrombus formation. The effect of vWF occurs primarily at high shear conditions typical intravascularly of flow at the apex of advanced stenotic lesions; thus, these findings may suggest that the absence of vWF may be protective against the development of acute thrombosis in these regions.
Cesarean Delivery in Relation to Birth Weight and Gestational Glucose Tolerance
Authors: C D Naylor, M Sermer, E Chen, K Sykora
Journal: JAMA (1996)

To examine the relationship between birth weight and mode of delivery among women with untreated borderline gestational diabetes mellitus (GDM), treated overt GDM, and normoglycemia.Prospective cohort study.Three Toronto, Ontario teaching hospitals.A total of 3778 volunteers aged 24 years or older.Subjects underwent a 3-hour long, 100-g oral glucose tolerance test at 28 weeks' gestation, regardless of screening test results. Usual care was provided to 143 women who met the National Diabetes Data Group criteria for GDM. Physicians were blinded to glucose tolerance test results for all others, including 115 untreated women with borderline GDM by the broader criteria of Carpenter and Coustan.Crude and adjusted rates of cesarean delivery and neonatal macrosomia (birth weight >4000 g).Compared with normoglycemic controls, the untreated borderline GDM group had increased rates of macrosomia (28.7% vs 13.7%, P<.001) and cesarean delivery (29.6% vs 20.2%, P=.02). Cesarean delivery in this subgroup was associated with macrosomia (45.5% vs 23.5%, P=.03). Usual care of known GDM normalized birth weights, but the cesarean delivery rate was about 33% whether macrosomia was present or absent. A clearly increased risk of cesarean delivery among treated patients compared with normoglycemic controls persisted after adjustment for multiple maternal risk factors (adjusted odds ratio, 2.1; 95% confidence interval, 1.3 to 3.6).Infant macrosomia was a mediating factor in high cesarean delivery rates for women with untreated borderline GDM. While detection and treatment of GDM normalized birth weights, rates of cesarean delivery remained inexplicably high. Recognition of GDM may lead to a lower threshold for surgical delivery that mitigates the potential benefits of treatment.
Aorta-Pulmonary Artery Communication Through the Lungs
Authors: T. STERLING CLAIBORNE, WILLIAM A. HOPKINS
Journal: Circulation (1956)

A case is reported of anomalous communication between the aorta and pulmonary artery by way of a pulmonary vascular mass. The left-to-right shunt was sufficient to cause typical circulatory dynamics and was demonstrated by cardiac catheterization and angiography. Complete cure was obtained by lobectomy.
Lysophosphatidic Acid Is a Major Regulator of Growth-Regulated Oncogene α in Ovarian Cancer
Authors: Zendra Lee, Ramona F. Swaby, Yuewei Liang, Shuangxing Yu, Shuying Liu, Karen H. Lu, Robert C. Bast, Gordon B. Mills, Xianjun Fang
Journal: Cancer Research (2006)

Abstract Growth-regulated oncogene α (GROα), a member of the chemokine superfamily, is commonly expressed in transformed cells and contributes to angiogenesis and tumorigenesis. Here, we report that increased GROα levels are detected in the plasma and ascites of ovarian cancer patients. Ovarian cancer cell lines in culture express and secrete GROα. However, when they are starved in serum-free medium, ovarian cancer cells ceased producing GROα, suggesting that GROα is not constitutively expressed but rather is produced in response to exogenous growth factors in ovarian cancer cells. The prototype peptide growth factors present in serum such as platelet-derived growth factor, insulin-like growth factor I, and insulin do not stimulate GROα production by ovarian cancer cells. In contrast, lysophosphatidic acid (LPA), a glycerol backbone phospholipid mediator present in serum and ascites of ovarian cancer patients, is a potent inducer of GROα expression in ovarian cancer cell lines. Treatment of ovarian cancer cells with LPA leads to transcriptional activation of the GROα gene promoter and robust accumulation of GROα protein in culture supernatants. The action of LPA on GROα expression is mediated by LPA receptors, particularly the LPA2 receptor in that ectopic expression of these receptors restores the LPA-dependent GROα production in nonresponsive cells. Down-regulation of LPA2 expression by small interfering RNA (siRNA) in ovarian cancer cells desensitizes GROα production in response to LPA. The effect of serum on GROα production is also significantly decreased by siRNA inhibition of LPA2 expression. These studies identify LPA as a primary regulator of GROα expression in ovarian cancer. (Cancer Res 2006; 66(5): 2740-8)
Acetylation of C/EBPε is a prerequisite for terminal neutrophil differentiation
Authors: Marije Bartels, Anita M. Govers, Veerle Fleskens, Ana Rita Lourenço, Cornelieke E. Pals, Stephin J. Vervoort, Rogier van Gent, Arjan B. Brenkman, Marc B. Bierings, Steven J. Ackerman, Jorg van Loosdregt, Paul J. Coffer
Journal: Blood (2015)
The nature of peptide interactions with acid end-group PLGAs and facile aqueous-based microencapsulation of therapeutic peptides
Authors: Andreas M. Sophocleous, Kashappa-Goud H. Desai, J. Maxwell Mazzara, Ling Tong, Ji-Xin Cheng, Karl F. Olsen, Steven P. Schwendeman
Journal: Journal of Controlled Release (2013)
More on Patients with Implantable Cardioverter-Defibrillators
Authors: John M. Embil
Journal: Annals of Internal Medicine (1995)

Letters1 December 1995More on Patients with Implantable Cardioverter-DefibrillatorsJohn M. Embil, MD, FRCPC and John S. Geddes, BSc, MD, FRCPJohn M. Embil, MD, FRCPCUniversity of Manitoba Health Sciences Centre; Winnepeg, Manitoba R3E 073; CanadaSearch for more papers by this author and John S. Geddes, BSc, MD, FRCPUniversity of Manitoba Health Sciences Centre; Winnepeg, Manitoba R3E 073; CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-11-199512010-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Pinski and Trohman [1] address key issues of concern to both the electrophysiologist and nonelectrophysiologist regarding implantable cardioverter-defibrillators. An additional aspect is that of patients returning to work after the implantation of a cardioverter-defibrillator.We have reported [2] the case of a male are welder with ventricular tachycardia that was refractory to medication. He initially refused implantation of such a device because his safety at work after implantation could not be guaranteed, and he was anxious about not being able to return to his place of employment. Because of ongoing ventricular tachycardia, the patient consented to having ...References1. Pinski SL, Trohman RG. Implantable cardioverter-defibrillators: implications for the nonelectrophysiologist. Ann Intern Med. 1995; 122:770-7. Google Scholar2. Embil JM, Geddes JS, Foster D, Sandeman D. Return to arc welding following defibrillator implantation. Pace Pacing Clin Electrophysiol. 1993; 16:2313-8. Google Scholar3. Fetter J, Benditt DG, Stauton MS. EMI effects from welding and motors on ICDS as tested in the hostile worksite [Abstract]. Circulation. 1994; 90:I498. Google Scholar Author, Article, and Disclosure InformationAuthors: John M. Embil, MD, FRCPC; John S. Geddes, BSc, MD, FRCPAffiliations: University of Manitoba Health Sciences Centre; Winnepeg, Manitoba R3E 073; Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1995Volume 123, Issue 11Page: 892-893KeywordsImplantable cardioverter defibrillatorsSafetyVentricular tachycardia ePublished: 15 August 2000 Issue Published: 1 December 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Acute Lung Injury Following Treatment With High-Dose Cyclophosphamide, Cisplatin, and Carmustine: Pharmacodynamic Evaluation of Carmustine
Authors: R. B. Jones, S. Matthes, E. J. Shpall, J. H. Fisher, S. M. Stemmer, C. Dufton, J. K. Stephens, S. I. Bearman
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Acute Lung Injury Following Treatment With High-Dose Cyclophosphamide, Cisplatin, and Carmustine: Pharmacodynamic Evaluation of Carmustine Get access Roy B. Jones, Roy B. Jones Bone Marrow Transplant Program, Division of Hematology/Oncology, University of Colorado Health Sciences CenterDenver, Colo Correspondence to: Roy B. Jones, Ph.D., M.D., Director, Bone Marrow Transplant Program, University of Colorado Health Sciences Center, Box B-190, 4200 East 9th Ave., Denver, Co 80262. Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven Matthes, Steven Matthes Bone Marrow Transplant Program, Division of Hematology/Oncology, University of Colorado Health Sciences CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth J. Shpall, Elizabeth J. Shpall Bone Marrow Transplant Program, Division of Hematology/Oncology, University of Colorado Health Sciences CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar James H. Fisher, James H. Fisher Division of Pulmonary Diseases, Department of Medicine, University of Colorado Health Sciences CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar Salomon M. Stemmer, Salomon M. Stemmer Bone Marrow Transplant Program, Division of Hematology/Oncology, University of Colorado Health Sciences CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar Christopher Dufton, Christopher Dufton Bone Marrow Transplant Program, Division of Hematology/Oncology, University of Colorado Health Sciences CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet K. Stephens, Janet K. Stephens Department of Pathology and the Cancer Center, University of Colorado Health Sciences CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar Scott I. Bearman Scott I. Bearman Bone Marrow Transplant Program, Division of Hematology/Oncology, University of Colorado Health Sciences CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 8, 21 April 1993, Pages 640–647, https://doi.org/10.1093/jnci/85.8.640 Published: 21 April 1993 Article history Received: 02 September 1992 Revision received: 31 December 1992 Accepted: 11 January 1993 Published: 21 April 1993
"CATARACT EXTRACTIONS PERFORMED BY PROF. JOSEF MELLER OF VIENNA 1919-1921"
Authors: Henry Smith
Journal: JAMA (1923)

To the Editor:  —I have just received the presession book of the Section on Ophthalmology containing the paper on cataract read by Dr. Hans Barkan at the recent annual session of the American Medical Association [The Journal, this issue, p. 2086]. I have not personally had the pleasure of meeting either Dr. Barkan or Dr. Meller.  The facts are not Dr. Barkan's but are those of Dr. Meller, and they seem to me to deserve some comment. The paper deals with 249 extractions; of these, 174 are treated in a separate group as uncomplicated. The remainder, amounting to no less than 30 per cent., are treated as complicated. Why reject to a category on which no reputation is to be based as many as 30 per cent.? It is more than three times as many as we encounter in practice, unless we are scouring up the cases rejected by every
Exome sequencing identifies the cause of a mendelian disorder
Authors: Sarah B Ng, Kati J Buckingham, Choli Lee, Abigail W Bigham, Holly K Tabor, Karin M Dent, Chad D Huff, Paul T Shannon, Ethylin Wang Jabs, Deborah A Nickerson, Jay Shendure, Michael J Bamshad
Journal: Nature Genetics (2009)
Induction of anti-allo-class I H-2 tolerance by inactivation of CD8+ helper T cells, and reversal of tolerance through introduction of third-party helper T cells.
Authors: S Kitagawa, S Sato, S Hori, T Hamaoka, H Fujiwara
Journal: The Journal of Experimental Medicine (1990)

The intravenous sensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) spleen cells resulted in the abrogation of CD8+ T cell-mediated anti-bm1 (proliferative and interleukin 2-producing) T helper (Th) cell activities. In vitro stimulation of lymphoid cells from these mice with bm1 cells, however, generated a reduced, but appreciable, anti-bm1 cytotoxic T lymphocyte (CTL) response. Moreover, the anti-bm1 CTL response, upon stimulation with [bm1 x B6-C-H-2bm12 (bm12)]F1 spleen cells, was enhanced when compared with the response induced upon stimulation with bm1 cells. These in vitro results were reflected on in vivo graft rejection responses; bm1 skin grafts engrafted in the bm1-presensitized B6 mice exhibited prolonged survival, whereas (bm1 x bm12)F1 grafts placed collateral to bm1 grafts (dual engrafted mice) inhibited the tolerance to bm1. In the B6 mice 1-2 d after rejecting the bm1 grafts, anti-bm1 Th activities remained marginal, whereas potent anti-bm1 CTL responses were found to be generated from their spleen cells. Administration in vivo of anti-CD4 antibody into bm1-presensitized, dual graft-engrafted mice prolonged bm1 graft survival and interfered with enhanced induction of anti-bm1 CTL activity. These results indicate that anti-class I alloantigen (bm1) tolerance as induced by intravenous presensitization with the relevant antigens is not ascribed to the elimination of CD8+ CTL precursors, but to the specific inactivation of CD8+ Th cells, whose function can be bypassed by activating third-party Th cells.