tbuckley/cabot-search huggingface dataset:
Patients with chronic myeloid leukemia treated with imatinib who showed the appearance of clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells
Authors: M M da Rocha, L Otero, T F Padilha, J Dobbin, C de Souza Fernandez, E Abdelhay, T de Souza Fernandez
Journal: Blood Cancer Journal (2011)

Chronic myeloid leukemia (CML) is a myeloproliferative disorder, characterized by the presence of the Philadelphia (Ph) chromosome, a consequence of a reciprocal translocation between chromosomes 9 and 22, resulting in the fusion of the genes BCR and ABL.The BCR-ABL fusion gene encodes a constitutively active leukemogenic protein tyrosine kinase.BCR-ABL kinase activity is inhibited by the selective activity of imatinib, a target agent that has demonstrated remarkable efficacy and tolerability. 1It has been shown that imatinib blocks cell proliferation and induces apoptosis in BCR-ABL-expressing hematopoietic cells.Imatinib has been used as a first line therapy for CML patients. 2Different patterns of response to imatinib treatment have been recognized, ranging from bestcase scenarios of rapid and unwavering response to difficult situations of intolerance and resistance, either primary or secondary. 3In general, most patients under imatinib achieve a major or complete cytogenetic response (CCyR), with restoration of a Ph-negative hematopoiesis.5][6][7] In this study, we describe four cases of CML patients treated with imatinib.These patients showed cytogenetic response with the disappearance of Ph-positive cells, but they acquired other clonal chromosomal abnormalities.In three cases, we had an extra chromosome Y and, in one case, the trisomy of 8. To our knowledge, this is the first study that discusses the acquisition of an extra chromosome Y in patients treated with imatinib who had cytogenetic response.Between 2000 and 2010 we studied, cytogenetically and clinically, 100 patients with CML, who were treated with imatinib at National Cancer Institute, Rio de Janeiro, Brazil.At the beginning of the therapy with imatinib, 66 patients were in chronic phase (CP), 24 patients in accelerated phase (AP) and 10 in blast crisis (BC).These patients were previously treated with hydroxyurea and interferon-a.There were 57 males and 43 females.The mean age of our patients were 48 years old (range from 14 to 75 years old).These patients were monitored by cytogenetic and molecular analyses during the treatment with imatinib.This study was reviewed and approved by the Ethical Committee from National Cancer Institute and it was in accordance with the Helsinki Declaration of 1975.Karyotypes of bone marrow cells were obtained from cultures in RPMI 1640 with 20% fetal calf serum at 37 1C for 24 h.Cell cultures were pulsed with colcemid.Cells were subsequently harvested by standard procedures and fixed in methanol-acetic acid.The chromosomes were analyzed by G-banding.The cytogenetic response was defined by the percentage of cells in metaphase, which was positive for the Ph chromosome in the bone marrow. 1 Fluorescence in situ hybridization (FISH) analysis was applied to fixed cell suspensions.
Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia
Authors: Marco Montillo, Salvatore Mirto, Maria Concetta Petti, Roberto Latagliata, Silvana Magrin, Antonio Pinto, Vittorina Zagonel, Giuseppina Mele, Alessandra Tedeschi, Felicetto Ferrara
Journal: American Journal of Hematology (1998)

Thirty-eight patients with primary resistant or relapsing acute myeloid leukemia (AML) were treated with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). Median age was 41 (range 11–70). Sixteen patients had AML that was primary resistant to induction treatment, while 22 were relapsed, 11 after autologous bone marrow transplant (AuBMT), 8 less than 6 months from complete remission (CR) achievement, and 3 were second relapse from chemotherapy alone. Overall, 21 of 38 patients (55%) obtained CR. Age, sex, length of CR, and interval between autoBMT and FLAG administration did not significantly influence the CR rate. On the contrary, a normal karyotype at diagnosis was significantly related to a better outcome. There were 4 induction deaths (10%), due to fungal infection in 2 patients and hemorrhagic complications in the remaining two. All patients experienced profound cytopenia. Median time to neutrophil (>500/μl) recovery was 21 days, while a platelet count >20,000/μl was reached after 23 days. The median period of hospitalization was 31 days. The nonhematological toxicity was mild, mainly consisting of mucositis. There were 17 documented infections and 17 episodes of fever of unknown origin. Following CR achievement, 6 patients received autoBMT, 3 alloBMT, 2 high-dose arabinosil-cytosine, and 2 are on a waiting list for transplantation procedure. We conclude that FLAG is an effective and well-tolerated regimen for refractory or recurrent AML, mainly useful for patients to be admitted to bone marrow transplantation. Am. J. Hematol. 58:105–109, 1998. © 1998 Wiley-Liss, Inc.
A RETRACTING TONSILLAR TONGUE DEPRESSOR
Authors: T. Carroll Davis
Journal: JAMA (1926)

Tongue depressors have been made in great numbers and varieties, but none seemed quite adequate for tonsillar work. The one described here I designed about two years ago and have found it very satisfactory. It has a shoulder and notch near the tip, as shown in the illustration. The shoulder is placed between the tongue and the jaw, and the notch then allows free access to the tonsil. The ends are made for right and left, and the shoulder helps hold when that end is used as a handle. It has three great advantages: The shoulder, being placed between the jaw and the tongue, not only depresses the latter but also retracts it. This enables the operator to get a view of the lower portion of the tonsil and of the tonsillar cavity when the tonsil has been removed. The shoulder also anchors the depressor so that it is not
Adenovirus-Mediated Transfer of a Minigene Expressing Multiple Isoforms of VEGF Is More Effective at Inducing Angiogenesis Than Comparable Vectors Expressing Individual VEGF cDNAs
Authors: Paul R Whitlock, Neil R Hackett, Philip L Leopold, Todd K Rosengart, Ronald G Crystal
Journal: Molecular Therapy (2004)

To assess the hypothesis that angiogenic gene therapy with the genomic form of vascular endothelial growth factor (VEGF) expressing the three major isoforms could be more potent than a vector expressing a single isoform, we designed an adenovirus vector (AdVEGF-All) expressing a VEGF cDNA/genomic hybrid gene. AdVEGF-All expressed all three major isoforms (121, 165, 189) in a 2:2:1 ratio. AdVEGF-All was 100-fold more potent than cDNA vectors expressing VEGF 121, 165, or 189 in restoring blood flow to the ischemic mouse hind limb. Interestingly, a mixture of Ad vectors individually expressing the VEGF 121, 165, and 189 cDNAs was equipotent to an equivalent dose of AdVEGF-All. Thus, a mixture of VEGF isoforms provides a more potent angiogenic response than a single isoform, suggesting that the individual isoforms function synergistically, an observation with important implications for gene and recombinant protein therapy.
Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride
Authors: Ogyi Park, Won-IL Jeong, Lei Wang, Hua Wang, Zhe-Xiong Lian, Eric M. Gershwin, Bin Gao
Journal: Hepatology (2008)

Abstract Liver fibrosis is a common scarring response to all forms of chronic liver injury and is always associated with inflammation that contributes to fibrogenesis. Although a variety of cell populations infiltrate the liver during inflammation, it is generically clear that CD8 T lymphocytes promote while natural killer (NK) cells inhibit liver fibrosis. However, the role of invariant natural killer T (iNKT) cells, which are abundant in the liver, in hepatic fibrogenesis, remains obscure. Here we show that iNKT-deficient mice are more susceptible to carbon tetrachloride (CCl 4 )-induced acute liver injury and inflammation. The protective effect of naturally activated iNKT in this model is likely mediated via suppression of the proinflammatory effect of activated hepatic stellate cells. Interestingly, strong activation of iNKT through injection of iNKT activator α-galactosylceramide (α-GalCer) accelerates CCl 4 -induced acute liver injury and fibrosis. In contrast, chronic CCl 4 administration induces a similar degree of liver injury in iNKT-deficient and wild-type mice, and only a slightly higher grade of liver fibrosis in iNKT-deficient mice than wild-type mice 2 weeks but not 4 weeks after CCl 4 injection, although iNKT cells are able to kill activated stellate cells. An insignificant role of iNKT in chronic liver injury and fibrosis may be attributable to hepatic iNKT cell depletion. Finally, chronic α-GalCer treatment had little effect on liver injury and fibrosis, which is attributable to iNKT tolerance after α-GalCer injection. Conclusion: Natural activation of hepatic iNKT cells inhibits, whereas strong activation of iNKT cells by α-GalCer accelerates CCl 4 -induced acute liver injury, inflammation, and fibrosis. During chronic liver injury, hepatic iNKT cells are depleted and play a role in inhibiting liver fibrosis in the early stage but not the late stage of fibrosis. (Hepatology 2009.)
Inhibition of integrin function by a cyclic RGD-containing peptide prevents neointima formation.
Authors: H Matsuno, J M Stassen, J Vermylen, H Deckmyn
Journal: Circulation (1994)

BACKGROUND RGD-containing peptides are able to prevent binding of ligands to certain integrins such as alpha IIb beta 3 (glycoprotein IIb/IIIa) and alpha v beta 3 and as such are inhibitors for platelet aggregation and smooth muscle cell migration, both of which are involved in neointima formation. METHODS AND RESULTS Hamster carotid arteries were damaged, and neointima formation was determined at different time points. G4120, a cyclic RGD-containing peptide, was administered continuously intravenously by an implanted osmotic pump. Neointima formation was inhibited dose dependently. The inhibition was strongest when treatment was started before the vascular injury and continued for the full observation period. Treatment started after the damage and maintained until neointima assessment or started before and stopped earlier was less effective. CONCLUSIONS Inhibition of integrin function by an RGD-containing peptide results in reduction of the development of a neointima. This effect is due both to an early event, which could be due to inhibition of secretion of PDGF by the platelets with blocked alpha IIb beta 3, and to a late event, possibly by interference with smooth muscle cell alpha v beta 3.
HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C
Authors: Rasmi Thomas, Richard Apps, Ying Qi, Xiaojiang Gao, Victoria Male, Colm O'hUigin, Geraldine O'Connor, Dongliang Ge, Jacques Fellay, Jeffrey N Martin, Joseph Margolick, James J Goedert, Susan Buchbinder, Gregory D Kirk, Maureen P Martin, Amalio Telenti, Steven G Deeks, Bruce D Walker, David Goldstein, Daniel W McVicar, Ashley Moffett, Mary Carrington
Journal: Nature Genetics (2009)
New procedure will speed up approval for embryo screening
Authors: Kunal Khanna
Journal: BMJ (2005)

Clinics with experience in screening embryos will have their applications to perform pre-implantation genetic diagnosis fast tracked under new procedures, the government's fertility watchdog announced last week.

Applications to perform pre-implantation genetic diagnosis may be approved without first having to go through the lengthy application process of the licence committee of the Human Fertilisation and Embryology Authority (HFEA), as long as the applying clinic has proven expertise in performing embryo biopsies and wishes to screen for a condition already being successfully tested for in another clinic. Such …
Reviews and Notes: Informatics: A History of Medical Informatics in the United States: 1950 to 1990
Authors: William Hersh
Journal: Annals of Internal Medicine (1996)

Literature of Medicine15 May 1996Reviews and Notes: Informatics: A History of Medical Informatics in the United States: 1950 to 1990William Hersh, MDWilliam Hersh, MDOregon Health Sciences University, Portland, OR 97201Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-10-199605150-00044 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail MF Collen. 489 pages. Bethesda, MD: Amer Med Informatics Assoc; 1995. $40.00. ISBN 0-9647743-0-5. Order phone 301-657-1291.The number of books on the applications of computers in medicine is growing, and most of these books are devoted to the technical or usage issues related to information machines and the clinicians who use them. This new book by Dr. Morris Collen is quite different, however. It presents an historic overview on the use of information technology in health care from the first applications in the 1950s to 1990. Collen played a significant role in developing several of these applications and is ... Author, Article, and Disclosure InformationAffiliations: Oregon Health Sciences University, Portland, OR 97201 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 1996Volume 124, Issue 10Page: 937KeywordsComputer applicationsComputer softwareComputersElectronic medical recordsHealth careHealth informaticsHealth information technologyInformation technologyPatients ePublished: 15 August 2000 Issue Published: 15 May 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Studies of a Patient with Megaloblastic Anemia and an Abnormal Transcobalamin II
Authors: Paul A. Seligman, LaDonna L. Steiner, Robert H. Allen
Journal: New England Journal of Medicine (1980)

TRANSCOBALAMIN II, a 38,000-dalton plasma protein, has a single binding site for cobalamin (vitamin B12) and functions as the major protein for transporting cobalamin to various tissues.1 2 3 4 Table 1 lists the characteristics of four cases of hereditary absence of transcobalamin II as previously described.5 6 7 These characteristics suggested simple cobalamin deficiency, but since about 70 to 90 per cent of the endogenous cobalamin in serum is found on cobalamin-binding proteins known as R proteins, 1 and only 10 to 30 per cent of serum cobalamin is bound to transcobalamin II, the serum cobalamin levels were all considered normal. All the patients had . . .
"AUROTHERAPY IN RHEUMATOID ARTHRITIS"
Authors: J. Albert Key
Journal: JAMA (1941)

<h3>To the Editor:—</h3> Your editorial on aurotherapy in rheumatoid arthritis (The Journal, August 2, p. 368) does not seem to me a fair statement of the present status of gold therapy either in this country or in England. At the last meeting of the American Rheumatism Association an entire morning was devoted to this subject. I believe the majority of the members of that association now agree that gold therapy is the treatment of choice for atrophic arthritis and think that it is especially valuable in early cases. As far as my associates and I can determine, gold is the only known drug that specifically influences the course of atrophic arthritis in a favorable manner. Since our paper on this subject was written we have continued to use gold, and by reducing the weekly dosage to 0.05 Gm. of sodium gold thiomalate, which contains 50 per cent gold, we have
COMPARISON OF ATRIAL FIBRILLATION ABLATION BLEEDING AND THROMBOTIC COMPLICATIONS WITH DABIGATRAN, RIVAROXABAN AND WARFARIN
Authors: Michael Bernard, William Brabham, Peter Netzler, Christopher Rowley, Michael Gold, Robert Leman, John Sturdivant, J. Marcus Wharton, Frank Cuoco
Journal: Journal of the American College of Cardiology (2013)
Assessment of a Pulmonary Origin for Blood Outgrowth Endothelial Cells by Examination of Identical Twins Harboring a <i>BMPR2</i> Mutation
Authors: Mark L. Ormiston, Laura Southgate, Carmen Treacy, Joanna Pepke-Zaba, Richard C. Trembath, Rajiv D. Machado, Nicholas W. Morrell
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Letting intrauterine devices lie.
Authors: W G Mills
Journal: BMJ (1982)

in the first 12 months,7 a comparison of the curves beginning after year 1 may be con- founded by variables related to survival.A number of presumably high-risk patients in the beta-blocker group were saved in the first year, most probably resulting in a patient population on that treatment which was, on average, sicker than that on placebo after one year.Thus, parallel and even converging curves beyond one year could be consistent with continued benefit.In addition, we do not know what would happen if the treatment were stopped at one year.Rose9 has posed the question, "Do beta-blockers merely keep the wolf from the door, and when protection is withdrawn, does he retum ?"We tend to conclude from the absolute difference in the number of deaths between the beta-blocker and placebo groups at the end of a trial how many lives had been prolonged.The results from the Norwegian timolol trial could imply that 54 deaths (152 minus 98) were delayed by an average of at least 17 months.Another interpretation could be that more than 150 patients had their lives prolonged by an average of six months.We have no way of knowing with certainty over what period of time during the entire patient follow-up protection is provided-that is, when the door is closed on the wolf.For these reasons, it seems prudent to recommend beta-blocker treatment to survivors of a heart attack for at least three years, the duration of the trial7 which followed patients for the longest time.
Extent of Deterioration in Physical Condition during Postoperative Bed Rest and its Reversal by Rehabilitation
Authors: E. J. Bassey, P. H. Fentem
Journal: BMJ (1974)

A study has been made of changes in physical condition associated with bed rest and rehabilitation in hospital patients. It was found that after two weeks recumbent bed rest there was a significant decline in physical condition. It was also found that the better the initial physical condition the greater the decline. Rehabilitation was associated with an improvement in physical condition, which seemed to be related to the increased level of daily activity rather than to the absolute levels of physical condition.
Book Review Atlas of Heart Diseases: Cardiomyopathies, myocarditis, and pericardial disease (Vol. 2.) Edited by Walter H. Abelmann. Approximately 250 pp., illustrated. St. Louis, Mosby, 1995. $125. 1-878132-24-5 Atlas of Heart Diseases: Cardiopulmonary diseases and cardiac tumors (Vol. 3.) Edited by Samuel Z. Goldhaber. Approximately 250 pp., illustrated. St. Louis, Mosby, 1995. $125. 1-878132-23-7
Authors: Robert J. Hall
Journal: New England Journal of Medicine (1995)
Esophageal Motility Disorders and Strictures
Authors: H.-D. Allescher
Journal: Endoscopy (2000)

Pneumatic dilation is the initial treatment of first choice in patients with achalasia. To compare different treatment alternatives in patients with achalasia, four different strategies (laparoscopic Heller myotomy with fundoplication, thoracoscopic myotomy, pneumatic dilation, and botulinum toxin injection) were compared using a decision analysis (Markov) model. On the basis of quality-adjusted life years (QALYs), only thoracoscopic myotomy was less effective than the other three strategies, but pneumatic dilation proved to be the most effective for patients with a life expectancy of more than seven years. However, based on these data, an individualized approach to patients with achalasia is recommended [1].
Murine mast cells exposed to mercuric chloride release granule-associated N-acetyl-β-D-hexosaminidase and secrete IL-4 and TNF-α
Authors: Jaroslaw Dastych, Aurelia Walczak-Drzewiecka, Janina Wyczolkowska, Dean D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (1999)
Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer
Authors: Lucia Regales, Yixuan Gong, Ronglai Shen, Elisa de Stanchina, Igor Vivanco, Aviva Goel, Jason A. Koutcher, Maria Spassova, Ouathek Ouerfelli, Ingo K. Mellinghoff, Maureen F. Zakowski, Katerina A. Politi, William Pao
Journal: Journal of Clinical Investigation (2009)

EGFR is a major anticancer drug target in human epithelial tumors. One effective class of agents is the tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. These drugs induce dramatic responses in individuals with lung adenocarcinomas characterized by mutations in exons encoding the EGFR tyrosine kinase domain, but disease progression invariably occurs. A major reason for such acquired resistance is the outgrowth of tumor cells with additional TKI-resistant EGFR mutations. Here we used relevant transgenic mouse lung tumor models to evaluate strategies to overcome the most common EGFR TKI resistance mutation, T790M. We treated mice bearing tumors harboring EGFR mutations with a variety of anticancer agents, including a new irreversible EGFR TKI that is under development (BIBW-2992) and the EGFR-specific antibody cetuximab. Surprisingly, we found that only the combination of both agents together induced dramatic shrinkage of erlotinib-resistant tumors harboring the T790M mutation, because together they efficiently depleted both phosphorylated and total EGFR. We suggest that these studies have immediate therapeutic implications for lung cancer patients, as dual targeting with cetuximab and a second-generation EGFR TKI may be an effective strategy to overcome T790M-mediated drug resistance. Moreover, this approach could serve as an important model for targeting other receptor tyrosine kinases activated in human cancers.
Association of low body temperature and poor outcomes in patients admitted with worsening heart failure: a substudy of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial
Authors: Saeed Payvar, John A. Spertus, Alan B. Miller, S. Ward Casscells, Peter S. Pang, Faiez Zannad, Karl Swedberg, Aldo P. Maggioni, Kimberly J. Reid, Mihai Gheorghiade
Journal: European Journal of Heart Failure (2013)
Sterile microenvironment in prevention of wound infection.
Authors: J M Scott, J McLauchlan, H G Smylie
Journal: BMJ (1982)

A prospective controlled trial was carried out to assess the effect of using a wound isolator on reducing postoperative infection. A total of 291 patients undergoing hip pinning for fractures of the neck of femur entered the trial and were allocated at random to have their wound contained in a wound isolator (study group) or dressed with a standard gamma-irradiated adhesive dressing (control group). The bacteriological flora of the patient was monitored before, during, and after operation and that of the ward before and after. No significant difference was found in the flora of the wards in which the patients were nursed. On several occasions the source of the infective organism was traced to the ward but never to the theatre. The isolator prevented direct contamination and airborne cross-infection of the wound and appreciably reduced the rate of infection.
1041-97 Assessment of transmyocardial velocity distribution during high dose dobutamine stress echocardiography using myocardial velocity profile
Authors: Hideji Tanaka, Tomotsugu Tabata, Kenji Harada, Eriko Kimura, Akihiro Saito, Tetsuzo Wakatsuki, Masahiro Nomura, Susumu Ito
Journal: Journal of the American College of Cardiology (2004)
Illinois is to estimate savings from letting its employees import cheap drugs
Authors: D. Spurgeon
Journal: BMJ (2003)

The governor of Illinois has fired the latest salvo at the Bush administration's policy of opposing the importation of cheap drugs from Canada.

Rod Blagojevich has directed state officials to investigate how much money could be saved by allowing thousands of current and retired state employees to import prescription drugs from Canada.

The governor's action is part of an ongoing revolt against the high cost of drugs in the United States, which can be bought from 25% to 80% more cheaply abroad.

In July 2002 the US Senate …