tbuckley/cabot-search huggingface dataset:
Beneficial effects of combining a type II ATP competitive inhibitor with an allosteric competitive inhibitor of BCR-ABL for the treatment of imatinib-sensitive and imatinib-resistant CML
Authors: E Weisberg, X Deng, H G Choi, R Barrett, S Adamia, A Ray, D Moreno, A L Kung, N Gray, J D Griffin
Journal: Leukemia (2010)
Quantitation of Backflow in Patients with Aortic Insufficiency Using an Indicator Technic
Authors: HOMER R. WARNER, ALAN F. TORONTO
Journal: Circulation Research (1958)

A method is reported which permits the estimation of the time-course of backflow velocity in the descending aorta of patients with insufficiency of the aortic valve. Instantaneous back-velocities in excess of 100 cm./sec. have been observed. Evidence suggesting the existence of an oscillation in aortic flow during diastole in some patients is presented. An index to the "volume of backflow per stroke" is described.
Does Pay-for-Performance Improve the Quality of Health Care?
Authors: Mark A. Van Swol
Journal: Annals of Internal Medicine (2007)

Letters3 April 2007Does Pay-for-Performance Improve the Quality of Health Care?Mark A. Van Swol, MDMark A. Van Swol, MDFrom Self Regional Healthcare, Greenwood, South Carolina.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-146-7-200704030-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: In their recent article, Petersen and colleagues (1) provide an excellent introduction to pay-for-performance initiatives with a special emphasis on determining the proof for its effectiveness in the literature.I agree that more research needs to be done in this area, particularly in examining unintended negative outcomes of such a system. The authors propose an agenda for future research.Two additional areas must be considered for future research. First, documenting and reporting these data is the biggest hurdle in pay-for-performance programs and can be done only through some type of electronic health record, which is the greatest ...References1. Petersen LA, Woodard LD, Urech T, Daw C, Sookanan S. Does pay-for-performance improve the quality of health care? Ann Intern Med. 2006;145:265-72. [PMID: 16908917] LinkGoogle Scholar2. Valdes I, Kibbe DC, Tolleson G, Kunik ME, Petersen LA. Barriers to proliferation of electronic medical records. Inform Prim Care. 2004;12:3-9. [PMID: 15140347] MedlineGoogle Scholar3. Bodenheimer T. Primary care—will it survive? N Engl J Med. 2006;355:861-4. [PMID: 16943396] CrossrefMedlineGoogle Scholar4. Miller RH, West C, Brown TM, Sim I, Ganchoff C. The value of electronic health records in solo or small group practices. Physicians' EHR adoption is slowed by a reimbursement system that rewards the volume of services more than it does their quality. Health Aff (Millwood). 2005;24:1127-37. [PMID: 16162555] CrossrefMedlineGoogle Scholar5. Hillestad R, Bigelow J, Bower A, Girosi F, Meili R, Scoville R, et al. Can electronic medical record systems transform health care? Potential health benefits, savings, and costs. Health Aff (Millwood). 2005;24:1103-17. [PMID: 16162551] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Self Regional Healthcare, Greenwood, South Carolina.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDoes Pay-for-Performance Improve the Quality of Health Care? Laura A. Petersen , LeChauncy D. Woodard , Tracy Urech , Christina Daw , and Supicha Sookanan Does Pay-for-Performance Improve the Quality of Health Care? Laura A. Petersen Metrics 3 April 2007Volume 146, Issue 7Page: 538KeywordsConflicts of interestElectronic medical recordsForecastingHealth careHealth care qualityMotivationResearch design ePublished: 3 April 2007 Issue Published: 3 April 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Destruction of leishmania mexicana amazonensis amastigotes within macrophages in culture by phenazine methosulfate and other electron carriers
Authors: M Rabinovitch, J-P Dedet, A Ryter, R Robineaux, G Topper, E Brunet
Journal: The Journal of Experimental Medicine (1982)

Exposure of macrophages infected with Leishmania mexicana amazonensis to phenazine methosulfate (PMS) resulted in rapid damage and disappearance of the intracellular amastigotes without obvious ill effects to the host cells. The reduction of the percent infection was related to the concentration of PMS and to the duration of the pulse. Most Leishmania disappeared within 2 h of a 2-h pulse with 10 μM of the drug. In contrast, pretreatment of the macrophages with PMS followed by removal of the drug before infection did not result in disappearance of the parasites. The pH of the PMS medium markedly influenced the disappearance of Leishmania: maximum effect was observed at pH 8.0, while the effect was negligible at pH 6.3. The pH effect may be related to pseudobase formation by the PMS cation. Dose-response curves for PMS were similar for resident, elicited, or activated macrophages. Observations by time-lapse cinemicrography documented the explosion-like fragmentation of the amastigotes within 1-2 h of exposure of infected macrophages to the drug. Parasite-derived granules and vacuoles were seen to scatter within the parasitophorous vacuoles. This early damage to the parasites was confirmed by transmission electron microscopic observations. Infected macrophages incubated with PMS displayed detectable vacuolar fluorescence, indicating that PMS or a metabolite of PMS had access to the vacuoles. A series of other electron carriers, including phenyl methanes, phenazines, oxazines, a xanthene, and a naphthoquinone, given continuously for 18 h, also induced the disappearance of the Leishmania. The most potent was crystal violet, active at 70 nM. The presence of apolar substituents enhanced activity and this is probably related to increased permeation of the dyes. Finally, PMS, as well as other electron carriers examined, also reduced the growth of Leishmania promastigotes in culture. The results are compatible with a direct effect of the drugs on the intracellular amastigotes, involving only a permissive participation of the macrophages. We propose that the diverse agents destroy the amastigotes by redox-cycling generation of active oxygen metabolites at or near the parasites. Alternatively, the effect of the drugs could be mediated by toxic free radical reduction species of the drugs or by interference with electron flow or with the intermediary metabolism of Leishmania.
Frequent truncating mutations of STAG2 in bladder cancer
Authors: David A Solomon, Jung-Sik Kim, Jolanta Bondaruk, Shahrokh F Shariat, Zeng-Feng Wang, Abdel G Elkahloun, Tomoko Ozawa, Julia Gerard, DaZhong Zhuang, Shizhen Zhang, Neema Navai, Arlene Siefker-Radtke, Joanna J Phillips, Brian D Robinson, Mark A Rubin, Björn Volkmer, Richard Hautmann, Rainer Küfer, Pancras C W Hogendoorn, George Netto, Dan Theodorescu, C David James, Bogdan Czerniak, Markku Miettinen, Todd Waldman
Journal: Nature Genetics (2013)
Metabolic Effects of Dietary Sucrose and Fructose in Type II Diabetic Subjects
Authors: Domingos A Malerbi, Ellen Simone A Paiva, Ana Lucia Duarte, Bernardo L Wajchenberg
Journal: Diabetes Care (1996)

OBJECTIVE To investigate the metabolic effects of dietary fructose and sucrose in type II diabetic patients. RESEARCH DESIGN AND METHODS Sixteen well-controlled type II diabetic subjects were fed three isocaloric diets for 28 days each. The three diets provided 50–55, 15, and 30–35% of total energy from carbohydrate, protein, and fat, respectively. In one diet, 20% of total calories were derived from fructose; in another, 19% of total calories were derived from sucrose; and in the control diet, only 5% of daily calories were derived from sugars, all other carbohydrates being supplied as polysaccharides. RESULTS No significant differences were observed between either the fructose or the sucrose diet and the control polysaccharide diet in any of the measures of glycemic control, serum lipid levels, or insulin and C-peptide secretion. CONCLUSIONS Our data suggest that in the short and middle terms, high fructose and sucrose diets do not adversely affect glycemia, lipemia, or insulin and C-peptide secretion in well-controlled type II diabetic subjects.
Ranitidine and Hepatic Injury
Authors: MARCOS A. SOUZA LIMA
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 July 1986Ranitidine and Hepatic InjuryMARCOS A. SOUZA LIMA, M.D.MARCOS A. SOUZA LIMA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-1-140_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Since our previous report (1) we have seen another case of ranitidine-associated hepatitis. It prompted a review of reports of hepatotoxicity associated with ranitidine and cimetidine that have been entered into the computerized filing system of the Division of Drug Experience of the Food and Drug Administration. The files encompassed a period of about 2 years for ranitidine and 8 years for cimetidine. There were 45 reports of hepatic injury for ranitidine, but a cause-and-effect relationship could not be established with certainty because of the frequent use of multiple drugs and the lack of rechallenge. We elected...References1. SOUZA LIMA M. Hepatitis associated with ranitidine. Ann Intern Med. 1984;101:207-8. LinkGoogle Scholar2. FEINSTEINHORWITZ AR. Double standards, scientific methods and epidemiologic research. N Engl J Med. 1982;307:1611-7. CrossrefMedlineGoogle Scholar3. IRELANDCOLIN-JONESGEAR ADP. Ranitidine 150 mg twice daily vs 300 mg nightly in treatment of duodenal ulcers. Lancet. 1984;2:274-5. CrossrefMedlineGoogle Scholar4. BARRPIPER GD. Possible ranitidine hepatitis. Med J Aust. 1981-2:421. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFamotidine-Induced Mixed Hepatocellular JaundiceChange in Prescribing Patterns of Intravenous Histamine 2 -Receptor Antagonists Results in Significant Cost Savings without Adversely Affecting Patient CareOverview of Medical Therapy of Peptic Ulcer DiseaseGastrointestinal drugsZaltidine: An Effective but Hepatotoxic H 2 -Receptor AntagonistHepatotoxic and hepatoprotective potential of histamine (H2)-receptor antagonists 1 July 1986Volume 105, Issue 1Page: 140-140KeywordsComputersComputing systemsDrug administrationDrugsFood and Drug AdministrationHepatitis ePublished: 1 December 2008 Issue Published: 1 July 1986 PDF downloadLoading ...
Abstract 5121: Laminin 511 on human gastric carcinoma cells is a ligand for hepatic asialoglycoprotein receptor involved in liver metastasis
Authors: Suguru Ueno, Yoshiaki Nodera, Laura Santos Gomez, Nobuaki Higashi, Tatsuro Irimura
Journal: Cancer Research (2010)

Abstract – Background and Aim – Gastric cancer often metastasizes to the liver and galactose-type lectins were previously proposed to play an important role in hepatic metastases because intravenous administration of galactose at the time of surgical removal of gastric cancer was reported to extend the survival of the patients. Asialoglycoprotein receptor (Asgpr) is a galactose-type calcium-type lectin and a primary candidate molecule involved in this process. Variant cell lines of human gastric carcinoma, AZ521 cells, were obtained by sorting for high and low levels of cell surface bindings of recombinant Asgpr and designated as AZhigh and AZlow cells, respectively. The present report is to assess the metastatic potential of these cell lines and determine the ligand for Asgpr on the surfaces of these gastric carcinoma cells. – Materials and Methods – AZhigh and AZlow cells were injected into nude mice via portal vein and metastatic growth in the liver were evaluated 14 days later. AZhigh and AZlow cells were biotinylated at the cell surfaces and the lysates were prepared. Components bound to immobilized Asgpr were collected and analyzed by SDS-PAGE then differentially expressed components were subjected to MALDI-TOF MS analysis after trypsin digestion. Specific monoclonal antibodies specific for particular components such as laminin α5 chain were used to confirm the identified proteins from the carcinoma cells. – Results and Discussion – Metastatic growth in the liver was more prominent with AZhigh cells than AZlow cells. AZhigh cells adhered to immobilized Asgpr more rapidly than AZlow cells. From components eluted from immobilized Asgpr, laminin α5, β1, and γ1 chains were identified. By flow cytometric analysis, anti-human laminin α5 antibody bound to AZhigh cells but the binding to AZlow were negligible. Similar difference was observed by immunoprecipitation. Laminin α5 chain was also in the culture supernatants of AZhigh cells, but not those of AZlow cells. These results suggest that laminin 511 differentially expressed between AZhigh and AZlow cells and acted as the ligands for Asgpr. Further study focusing on laminin 511 will be needed for elucidating the mechanism of hepatic metastases of gastric cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5121.
SKIN REACTIONS TO ALTERNATE HEAT AND X-RAY EXPOSURES
Authors: James A. Hawkins, Harry Clark
Journal: The Journal of Experimental Medicine (1925)

Different areas on the abdomen of the same guinea pigs have been exposed to suberythema doses of soft x-rays, to heat of an intensity below the critical dose for the production of burns, and to both radiations in sequence. The only effect of exposure to x-ray or heat alone was a slight scaling of the skin. The areas exposed to heat and x-radiation developed well marked and persistent burns. The results were the same no matter in which sequence the agents were applied.
Abstract 4434: Combined targeting of Aurora B (AZD1152) and MEK1/2 (AZD6244) kinases leads to enhancement of anti-tumour effects <i>in vivo.</i>
Authors: Rajesh Odedra, Simon Heaton, Armelle Logie, Kirsten E. Mundt, Elizabeth Anderson, Paul D. Smith, Robert W. Wilkinson
Journal: Cancer Research (2010)

Abstract Future cancer treatment regimes may involve novel drug combinations aimed at targeting different pathways involved in tumour proliferation and survival. Understanding the mechanisms involved in such combinations and identifying the optimum schedule/sequence will be key to guiding clinical development. The Aurora kinases play a critical role in mitosis and have been suggested as promising targets for therapy due to their frequent over expression in a variety of tumours. AZD1152 is a selective Aurora B kinase inhibitor, with a novel anti-tumour mechanism of action, inducing endoreduplication, apoptosis and inhibition of cytokinesis. The MAPK signaling pathway is implicated in uncontrolled cell proliferation and cell survival in many cancers. AZD6244 (ARRY-142886), a selective, ATP non-competitive inhibitor of MEK1/2, has demonstrated G1 arrest and anti-tumour activity in a range of preclinical models. In the present study, we dosed AZD1152 and AZD6244 in combination to nude mice bearing human NSCLC tumour (Calu-6) xenografts. Pharmacodynamic analysis of Calu-6 xenografts treated with either AZD1152 or AZD6244 as monotherapies (MonTx) indicated downstream biomarker effects in accordance with their targets (for e.g. suppression of phosphorylation of histone H3 and ERK, respectively). When the same doses of AZD1152 (150mg/Kg/day s.c. for 2 days via osmotic minipumps) or AZD6244 (25mg/kg/BID p.o.) were dosed in a chronic disease setting, both drugs significantly suppressed Calu-6 tumour growth (versus respective vehicle groups, p&amp;lt;0.005). In combination, the two drugs were dosed in sequence, either AZD1152 → AZD6244 or AZD6244 → AZD1152. Whilst both sequences proved superior to the vehicle arms, only AZD1152 → AZD6244 proved superior to both MonTx arms in terms of apoptosis induction and tumour growth inhibition. These data indicate a promising therapeutic strategy for combining AZD1152 and AZD6244, and suggest that the sequence of drug administration may be critical when combining these inhibitors. Both AZD1152 and AZD6244 are currently in clinical trials. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4434.
The Familial Occurrence of Ankylosing Spondylitis
Authors: J. H. Jacobs, F. C. Rose
Journal: BMJ (1954)

This paper reports a family in which three brothers, one sister, and a paternal uncle suffered from ankylosing spondylitis, and discusses the importance of heredity in this condition.Although von Becterew and Marie described families with multiple cases of spondylitis, many observers since have believed that there was no familial predisposition in this disease.Llewellyn Jones (1909) said that heredi- tary transmission was extremely rare.Dunham and Kautz (1941) and Stone, as recently as 1947, made no reference to heredity in the aetiology of ankylosing spondylitis.MacWhirter (1945) stated that the disease may sometimes be familial.Simpson and Stevenson (1949), in an analysis of 200 cases, found a positive family history in only two patients-that is, a familial incidence of 1 %.Campbell (1947), in reporting 25 cases of ankylosing spondylitis, mentioned four families in which multiple cases of the disease had occurred, and said that " the family history is significant and inade- quately emphasized in the English literature."Stecher and Hauser (1946) reported four instances of ankylosing spondylitis affecting brothers, but were " forced to con- clude . . .such a coincidence may have resulted from chance alone."In 1952, however, Stecher reported 59 families with more than one person suffering from the disease, and stated that the incidence of ankylosing spondylitis in relatives of patients was 30 times that of controls.Families have also been reported by Ray (1931-2), Stauffer and Moffett (1946), Tegner and Lloyd (1949), Fraser (1950), and Riecker et al. (1950); the last-mentioned authors thought that transmission was probably due to an autosomal dominant gene.Hersh et al. (1950), in a study of 50 families of ankylosing spondylitis, concluded that " there can no longer be any reasonable doubt that heredity plays a major role in the aetiology of spondylitis."Case Reports Case 1.-A man of 27 had in 1946, when aged 18, suffered from an attack of low back pain which was treated with physiotherapy and went within a few weeks.He remained well until 1953, when he began to develop pain and stiffness in his cervical and dorsal spine, which gradually increased in severity.He had lost 21 lb.(9.5 kg.) in weight over the previous year.Examination revealed a generalized stiffness of his spine, most marked in the cervical region, and he could not reach within 16 in.(40.6 cm.) of his toes.His chest expansion was i in. (6mm.).His haemoglobin was 13.7 g. per 100 ml.; sedimentation rate (Westergren), 20 mm. at one hour.X-ray examination showed: chest normal; early ligamentous calcification of cervical spine; erosions and sclerosis on the left sacro-iliac joint, the right side appearing within normal limits.Case 11.-A male aged 29 was first seen in 1947, when aged 22, complaining of pain at the base of his spine of three months' duration.The pain was worse in bed at night and was relieved by getting up and walking.On examina-
Quels sont les résultats à long terme du traitement endoscopique et médical de la dysfonction du sphincter d'Oddi?
Authors: V Vitton, R Delpy, A Desjeux, M Gasmi, C Subtil, JC Grimaud, M Barthet
Journal: Endoscopy (2007)

Le traitement endoscopique de la dysfonction oddienne a une efficacité proche de 90% dans deux études prospectives. Toutefois les résultats à long terme et sa comparaison au traitement médical sont mal connus. Le but de notre travail était d'évaluer les résultats à long terme de la prise en charge endoscopique ou médicale de la dysfonction du sphincter d'Oddi.
Abstract 1948: Tissue accumulation and release of platinum from a novel chitosan-hybrid gel after intraperitoneal drug delivery
Authors: Sungpil Cho, Yongen Sun, Andrew P. Soisson, Mark K. Dodson, David K. Gaffney, C. Matthew Peterson, Margit-M Janat-Amsbury
Journal: Cancer Research (2012)

Abstract Gynecological malignancies such as cervical, endometrial and ovarian cancer still are the leading causes of death for women worldwide. However, standard therapies such as surgical cytoreduction and systemic chemotherapy combined with radiation have shown limited-efficacy by accessibility as well as nonspecific toxicity. To overcome those limitations, we previously reported about the development of a muco-adhesive, chitosan-hybrid gel (CS(BCDDP)) embedded with alginate beads containing cisplatin (CDDP) for a local, intraperitoneal application (# 3232, AACR 2011). Here we report the results of CDDP release from the (CS(BCDDP)), its cellular activity in vitro and CDDP accumulation to genomic DNA (gDNA) of tissues in vivo. To determine the amount of CDDP released from (CS(BCDDP)) in vitro, we used a colorimetric SnCl2 assay following the incubation in 0.9% NaCl solution for 24 hrs. (CS(BCDDP)) demonstrated successful release of 90% CDDP within 2 hrs and consistent CDDP-release could be maintained for up to 24 hrs. To test activity of CDDP released from (CS(BCDDP)), clonogenic assay was performed with Hela (human cervical adenocarcinoma) cells. Cells treated with (CS(BCDDP)) demonstrated a significantly low number of colonies, generating 9 (± 6) colonies per 500 cells seeded compared with 233 (± 10) colonies per 500 cells treated with an empty, no drug containing control gel (CS). To further assess CDDP accumulation to gDNA of tissues in vivo, inductively coupled plasma mass spectrometry (ICP-MS) was performed with tissue samples obtained from the left peritoneal sidewall of female nude mice following treatment with a control gel mixed with CDDP (CSCDDP), (CS(BCDDP)), and intravenously (i.v.) CDDP(CDDPIV). The results demonstrated a greater than three-time enhancement of CDDP-accumulation to the gDNA from (CS(BCDDP)) when compared to CDDPIV. Moreover, (CS(BCDDP)) also demonstrated higher accumulation of CDDP to gDNA when compared with CSCDDP. Relative values were 3.2 (±0.9) for (CS(BCDDP)) and 1.3 (± 0.4) for CSCDDP compared to values obtained from CDDPIV. Our in vitro and in vivo results, strongly suggest the feasibility of applying this hybrid gel locally to mucosal surfaces of the female reproductive tract and its advantage for intraperitoneal drug accumulation. Currently ongoing experiments are evaluating the efficacy and safety of our hybrid gel/CDDP in orthotopic endometrial, ovarian and cervical cancer animal models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1948. doi:1538-7445.AM2012-1948
Review: Noninvasive vs invasive weaning from mechanical ventilation reduces mortality in respiratory failure
Authors: Ronald G. Pearl
Journal: Annals of Internal Medicine (2014)

Source Citation Burns KE, Meade MO, Premji A, Adhikari NK. Noninvasive ventilation as a weaning strategy for mechanical ventilation in adults with respiratory failure: a Cochrane systematic review. CMAJ. 2014;186:E112-22. 24324020