tbuckley/cabot-search huggingface dataset:
Reply to A.A. Brandes et al
Authors: Patrick Y. Wen, Martin J. Van den Bent, David R. Macdonald, Michael A. Vogelbaum, Susan M. Chang
Journal: Journal of Clinical Oncology (2011)

We thank Brandes and Franceschi 1 for their thoughtful comments.We agree that the Response Assessment in Neuro-Oncology (RANO) criteria will require prospective validation in clinical trials, and we indicated this need in the conclusion of the article.The primary purpose of the article was to update the response criteria for high-grade gliomas in an era in which antiangiogenic agents were producing pseudoresponses and chemoradiotherapy was causing pseudoprogression, rendering the old Macdonald criteria obsolete.The optimal end points for phase II and III clinical trials in high-grade gliomas were not the focus of the RANO article but will be the subject of a separate report from the RANO Working Group.We agree that difficulties in assessing response and progression in patients receiving antiangiogenic therapies reduce the reliability of progression-free survival as an end point and that using overall survival as an end point has some advantages.Nonetheless, overall survival itself has its limitations, especially as more effective salvage therapies become available.
Intérêt des confrontations endoradiocinematographiques dans le diagnostic et le traitement de la Bilharziose urinaire
Authors: M. Jaupitre, A. Jaupitre
Journal: Endoscopy (1970)

Urinary bilharziosis is a very widely distributed disease; 150 million people are affected. The diagnosis of bilharziosis is made on clinical facts and upon biological findings. But two examinations are fundamental: cystoscopy and x-ray.
Recombinant Erythropoietin and Medicare Payment-Reply
Authors: Frank D. Gianfrancesco
Journal: JAMA (1991)

<h3>In Reply.</h3> —We have read with interest Dr Eggers' comments on our article. The article commended rather than criticized the HCFA for its initial payment policy. We expressed concern not with the initial policy but with its monitoring and refinement over time. The HCFA should have anticipated that a fixed payment rate per treatment for a non-life-threatening condition would create strong financial incentives for low dosing. Dialysis facilities have historically been responsive to the financial incentives of Medicare's fixed rate per dialysis treatment, eg, by reusing dialyzers.<sup>1</sup>One would thus have expected that their dosages of recombinant erythropoietin would also reflect financial incentives, as they apparently did. We appreciate Eggers' clarification of the system that the HCFA established to monitor use. Contrary to the information that we received previously, the HCFA's central office obtains from its intermediaries monthly billings that include individual patient's dosage and hematocrit levels (P. Eggers,
Postnephrectomy Arteriovenous Fistula
Authors: Stanley P. Silverblatt
Journal: JAMA (1967)

Twenty years after an uncomplicated right nephrectomy for hydronephrosis, a bruit on the right side of the flank, indicative of an acquired arteriovenous fistula, was first recorded. In late 1965 and early 1966, nearly 36 years after the original surgery, this postnephrectomy arteriovenous fistula was associated clinically with suspected bacterial endarteritis, proven concurrent bacterial endocarditis, and intractable congestive heart failure. In March 1966, the fistula was divided successfully. At the time of surgery, flow across the fistula was calculated and found to approximate 40% of the cardiac output. This postnephrectomy arteriovenous fistula is thought to represent the 15th example of this entity as reported in the medical and surgical literature and the first postnephrectomy arteriovenous fistula reported to be associated with bacterial endarteritis and bacterial endocarditis.
Coumarin Resistance in a Negro Woman
Authors: JAMES ZAGER
Journal: Annals of Internal Medicine (1973)

Letters1 May 1973Coumarin Resistance in a Negro WomanJAMES ZAGER, M.D., T. B. TJANDRAMAGA, M.D., S. A. CUCINELL, M.D., PETER G. DAYTON, D.SC.JAMES ZAGER, M.D.Search for more papers by this author, T. B. TJANDRAMAGA, M.D.Search for more papers by this author, S. A. CUCINELL, M.D.Search for more papers by this author, PETER G. DAYTON, D.SC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-775 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Two white families with hereditary coumarin resistance have been reported (1, 2). We found a 27-year-old negro woman who apparently has this trait. She had normal prothrombin time despite sodium warfarin therapy (Coumadin⌖, 15 to 20 mg/ day).Anticoagulation was tried in view of her mitral valve prosthesis with residual aortic regurgitation; paroxysmal tachycardia was controlled with quinidine sulfate (800 mg/day). She was also receiving digoxin, penicillin (for prophylaxis, to prevent recurrence of rheumatic fever), trichlormethiazide as a diuretic, and KC1 supplement. The oral anticoagulant was changed to bishydroxycoumarin (Dicoumarol⌖) for easier measurement of plasma levels (3)....References1. O'REILLY R: The second reported kindred with hereditary resistance to oral anticoagulant drugs. N Engl J Med 282:1448-1451, 1970 CrossrefMedlineGoogle Scholar2. O'REILLYAGGELER RP: Determinants of the response to oral anticoagulant drugs in man. Pharmacol Rev 22:35-96, 1970 MedlineGoogle Scholar3. AXELRODCOOPERBRODIE JJB: Estimation of dicumarol, 3, 3′-methylenebis (4-hydroxycoumarin) in biological fluids. Proc Soc Exp Biol Med 70:693, 1949 CrossrefMedlineGoogle Scholar4. WEINERSHAPIROAXELROD MSJ: The physiological disposition of dicumarol in man. J Pharmacol Exp Ther 99:409-416, 1950 MedlineGoogle Scholar5. NELSON T: Effect of dicumarol on blood vascular integrity in the rabbit. Circulation Res 8:889-896, 1960 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine Emory University School of Medicine Atlanta, Georgia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHigh clearance of (S)-warfarin in a warfarin-resistant subject.Familial Warfarin Resistance 1 May 1973Volume 78, Issue 5Page: 775-776KeywordsBlood plasmaCoumarinsDiureticsPenicillinProphylaxisProthrombin timeRheumatic feverSodiumSulfatesTachycardia Issue Published: 1 May 1973 PDF DownloadLoading ...
Response to Merin and Reeves
Authors: Francisco Gómez-Ulla, Maria I. Fernandez, Francisco Gonzalez, Pablo Rey, Marta Rodríguez, Maria J. Rodriguez-Cid, Felipe F. Casanueva, Maria A. Tome, Javier Garcia-Tobio, Francisco Gude
Journal: Diabetes Care (2003)

Prospective Diabetes Study Group: Intensive blood-glucose control with sulphonylurea
Abstract 4151: Mutual feedback activation of PI3K and MAPK pathways support combining inhibitors of the two pathways to enhance efficacy
Authors: Theresa Zhang, Igor Feldman, Cloud Paweletz, Michael Nebozhyn, Stuart Shumway Shumway, Albert Chen Chen, Brian Roberts Roberts, William Arthur, Sriram Sathyanarayanan, Bart Lutterbach, Peter Strack, Pearl Huang, Hongyue Dai, Andrey Loboda, James Watters
Journal: Cancer Research (2010)

Abstract There has been increasing interest in developing cancer therapies targeting PI3K pathway nodes. Unfortunately, the number of tumor types responding to PI3K pathway inhibitors as monotherapy has been limited, since most cancer cells accumulate genetic alterations that result in the constitutive activation of a complex network of proliferation and survival signals. As such, the inhibition of a single survival/proliferation pathway or node within this broader network may be circumvented by constitutive activation (or feedback activation) of an alternative survival pathway, and thus be insufficient for inducing a clinical response. Therefore, in most tumor types, dual pathway inhibition, guided by an in-depth understanding of feedback and cross-talk between pathways, may be required to induce tumor regression. Here we present a nonclinical study exploring mutual feedback activation of MAPK and PI3K pathways. Inhibition of the PI3K pathway by MK-2206 (AKT inhibitor) or MK-8669 (mTOR inhibitor) resulted in feedback activation of MAPK pathway nodes in subsets of lung cell lines. Similarly, inhibition of the MAPK pathway by a MEK inhibitor resulted in feedback activation of the PI3K pathway. Notably, a lack of such feedback activation was associated with sensitivity to the mono inhibitors. The strength of the feedback activation correlated with changes of several receptor tyrosine kinases, suggesting them as a part of the feedback mechanism. Finally, combined inhibition of both MAPK and PI3K pathways synergistically inhibited the feedback activation of both pathways and led to improved in vitro efficacy. Taken together, our findings identify mutual feedback activation of the PI3K and MAPK pathways in response to specific inhibitors and underscore the importance of combined therapeutic approaches with inhibitors to both pathways. 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 4151.
Patency of Infarct-Related Artery
Authors: Andrea Mortara, Giuseppe Specchia, Maria Teresa La Rovere, J. Thomas Bigger, Frank I. Marcus, John A. Camm, Stefan H. Hohnloser, Ryuji Nohara, Peter J. Schwartz
Journal: Circulation (1996)

In post-myocardial infarction (MI) patients, the restoration of anterograde flow in the infarct-related artery (IRA) significantly improves survival. Limitation of infarct size and increased electrical stability of the myocardium are likely operating mechanisms for this beneficial effect. We tested the hypothesis that patency of the IRA may enhance vagal reflexes, a factor known to affect electrical stability of the infarcted myocardium.Analysis of angiographic data was performed in 359 of 1284 post-MI patients enrolled in a multicenter prospective study within 8 weeks after the index MI. All the patients underwent baroreflex sensitivity (BRS) assessment by the phenylephrine method. The BRS of the entire population averaged 8.2+/-5.5 ms/mm Hg and was significantly related to age but not to ejection fraction (EF). One-, two-, and three-vessel disease was present in 138, 96, and 99 patients, respectively, while no coronary stenosis was observed in 26. IRA patency was documented in 234 patients (65%), while in the remaining 125 (35%), the artery remained occluded. Patients with occluded IRAs had more extensive coronary disease (2 to 3 vessels, 71% versus 46%, P<.01) and more depressed left ventricular (LV) function (LVEF, 48+/-13% versus 53+/-12%, P<.001). Patency of the IRA was associated with higher BRS values (BRS, 8.9+/-5.8 versus 7.1+/-4.7 ms/mm Hg, P<.005) and with a lower incidence (9% versus 18% P<.02) of markedly depressed BRS (<3 ms/mm Hg), a condition suggested by preliminary studies to be associated with an increased risk of post-MI mortality. The association between IRA patency and BRS was more evident in anterior than in inferior MI. Multivariate regression analysis showed that age of the patient and patency of the IRA were the major independent determinants of BRS, while LVEF was weakly related to BRS and only when analyzed as a categorized variable.The presence of an open IRA is associated with higher baroreflex sensitivity, and this effect is largely independent of limitation of infarct size by IRA patency. These data offer new insights into the mechanisms by which coronary artery patency may affect cardiac electrical stability and survival.
Abstract 2194: Tyrosyl DNA phosphodiesterase I is a prognostic factor and its inhibition synergizes response to topoisomerase poisons in malignant glioma.
Authors: Maha Al-Keilani, Supreet Agarwal, Mohammad Alqudah, Zita Sibenaller, Timothy Ryken, Mahfoud Assem
Journal: Cancer Research (2013)

Abstract Malignant Glioma is the most common type of primary brain tumors in adults accounting for about 80% of all gliomas. Despite the advances in treatment and diagnosis, the prognosis of malignant glioma is still poor with a median survival less than a year for glioblastoma patients. Targeting DNA-repair mechanisms is a clinically relevant option for enhancing response to DNA-damaging anticancer agents. TDP1 has been recently discovered to be responsible for the repair of the irreversible DNA-topoisomerase I covalent complexes produced by topoisomerase I poisons. Other studies have suggested its role in the repair of the DNA damage produced by ionizing radiation and temozolomide. However, TDP1 relevance has not yet been studied in glioma. Thus the aims of this project are to identify the role of TDP1 in glioma aggressiveness and resistance to therapies. We hypothesize that high-grade gliomas possess higher TDP1 levels which are associated with lower survival and resistance to therapy. Quantitative real-time PCR analysis of TDP1 in glioma biopsies revealed a negative prognostic effect of TDP1, where the level of TDP1 mRNA was inversely correlated with patient survival. Moreover, western blot showed an overexpression of TDP1 in glioma biopsies compared to normal tissues and increased expression with higher grades. TDP1 overexpression in U87 cell lines did not induce resistance to temozolomide, topotecan, etoposide or doxorubicin. This may be related to other downstream DNA repair enzymes that need to be also modulated to fully induce drug resistance. However, TDP1 inhibition using small molecules synergizes the cytotoxicity of topotecan, etoposide, and doxorubicin, confirming thus its critical role in response to several therapeutic agents. As a conclusion, TDP1 is a new and promising prognostic factor and a modulator of therapy response in malignant glioma that may help in stratification of patients. Additionally, targeting TDP1 is a novel strategy that will widen the therapeutic options for malignant glioma where topoisomerase I and II poisons can be part of the gold standard therapy when used in combination with TDP1 inhibitors. Citation Format: Maha Al-Keilani, Supreet Agarwal, Mohammad Alqudah, Zita Sibenaller, Timothy Ryken, Mahfoud Assem. Tyrosyl DNA phosphodiesterase I is a prognostic factor and its inhibition synergizes response to topoisomerase poisons in malignant glioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2194. doi:10.1158/1538-7445.AM2013-2194
Binge Eating and Purging in Young Women With IDDM
Authors: Terry Stancin, Diane L Link, jeanette M Reuter
Journal: Diabetes Care (1989)

Case reports and empirical studies suggest that young women with insulin-dependent diabetes mellitus (IDDM) may be at high risk for developing eating disorders. In this study, self-reports of binge eating and purging from 59 IDDM women (aged 18–30 yr) were obtained. Most participants (58%) reported that they went on eating binges, and 12% met the DSM-III criteria for a diagnosis of bulimia. Nearly 40% admitted to controlling their weight by insulin purging, and 13.5% reported purging by other means. A group of bulimic participants had mean scores on an eating disorder questionnaire in the pathological range. Bulimic symptoms were positively related to reports of hospitalizations, episodes of ketoacidosis, and psychological symptoms. Implications of these results on the medical management of young women with IDDM are discussed.
Abstract 891: The chemokine receptor CXCR7 transduces its signal through mTOR: the role of everolimus
Authors: Caterina Ieranò, Michele Caraglia, Francesca Bernile, Elena Antignani, Maria Napolitano, Anna Riccio, Luigi Portella, Mark E. Penfold, Stefania Scala
Journal: Cancer Research (2012)

Abstract Everolimus (RAD001, Afinitor) is an mTOR inhibitor FDA-approved for the treatment of patients with advanced clear cell renal cancer (RCC) after failure of treatment with sunitinib or sorafenib, or both drugs. It targets the mammalian target of rapamycin (mTOR) complex inhibiting a serine/threonine kinase regulating PI3K/AKT signaling pathway. Previous evidences demonstrated that the activation of the chemokine receptor CXCR4 involved the mTOR pathway and that CXCR4 was overexpressed in RCC. Recently, also the deorphanized chemokine receptor CXCR7 was described in RCC and defined as an independent prognostic factor. Nevertheless, little is known about the CXCR4-CXCL12-CXCR7-induced signalling. Aim of the study was to investigate if the CXCL12/CXCR4/CXCR7 complex could transduce the signal through mTOR identifying new therapeutic targets. In human renal cancer cells (RXF393, A498) treatment with CXCL12, the CXCR4 and CXCR7 ligand, induced mTOR pathway, as demonstrated through p70S6K and eukaryotic initiation factor 4E binding protein 1 (4E-BP1) induction; the CXCL12 induction is specifically inhibited by AMD3100, a CXCR4 inhibitor, and CCX733, a CXCR7 inhibitor. The inhibition of the mTOR pathway through RAD001 treatment, inhibited CXCL12-induced pERK1/2 and chemotaxis while AMD3100 and CCX733 were not able to inhibit pERK and migration in RXF393 and A498 cell lines suggesting a role of mTOR downstream of CXCR4 and CXCR7. To analyze the CXCR7 transduction pathway the function of p38 kinase, a CXCR7 target, was evaluated. CXCL12 dramatically induced p38 MAPK in cell lines RXF393 and A498 and the p38MAPK induction was specifically inhibited by CCX733, a CXCR7 inhibitory molecule but, interestingly, p38 MAPK is dramatically induced by AMD3100, a CXCR4 antagonist. To further confirm the p38 role downstream of CXCR7, CXCL12 was unable to induce p38 phosphorylation in RXF393 cells CXCR7 siRNA transduced while inhibited by the specific CXCR7 inhibitor CCX733 in RXF393 cells. The treatment with RAD001 in human renal cancer cells inhibited the p38 induction CXCL12-mediated. This is the first evidence demonstrating that p38 is a CXCR7 target in human renal cancer cells and that AMD3100, a specific CXCR4 antagonist, potentiate the CXCL12 activity on CXCR7. Thus the combined inhibition of the three members CXCR4/CXCR7/mTOR is a valid therapeutic strategy to treat RCC inhibiting two cross talking pathways CXCR4-CXCR7 signaling to mTOR. 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 891. doi:1538-7445.AM2012-891
THE PROLIFERATIVE AND ANAMNESTIC ANTIBODY RESPONSE OF RABBIT LYMPHOID CELLS IN VITRO
Authors: G. A. Theis, G. J. Thorbecke
Journal: The Journal of Experimental Medicine (1970)

Both primary and secondary responses to sheep erythrocytes and to Brucella abortus antigen have been obtained in cultures of dispersed rabbit spleen cells. Removal of adherent cells by repeated incubation of spleen cells on absorbent cotton diminished the ability of the spleen cell suspensions to give secondary as well as primary responses in vitro. When comparing cultures made in dishes and in tubes, the loss of responsiveness after incubation on cotton was much more evident in the dish cultures. It was concluded that the cell-to-cell interaction needed for immune responses to particulate antigens in vitro was more readily interfered with when the cells were spread over a larger surface area. The proliferative response to antigen, as measured by uptake of (3)H-thymidine in tube cultures of the sensitive spleen cells, appeared particularly resistant to the depletion effect of adherent cell removal. Dispersed spleen cells from sensitized mice gave a secondary response to sheep erythrocytes. This response was readily abolished by one incubation on absorbent cotton when the cells were cultured in dishes.
Progression to diabetes in relatives with islet autoantibodies. Is it inevitable?
Authors: S G Gardner, E A Gale, A J Williams, K M Gillespie, K E Lawrence, G F Bottazzo, P J Bingley
Journal: Diabetes Care (1999)

OBJECTIVE: A large cohort of family members with islet cell antibodies (ICA) &amp;gt; or = 20 Juvenile Diabetes Foundation units (JDF U) was examined to determine whether there was a subgroup at low risk of progression to diabetes; whether risk of progression changed over time; and whether rate of progression to diabetes varied according to age, islet autoantibodies, and genetic markers of susceptibility. RESEARCH DESIGN AND METHODS: Individuals with ICA &amp;gt; or = 20 JDF U were identified from 4,423 family members recruited to prospective family studies in the U.K. Subjects were followed for up to 18 years. Antibodies to insulin, GAD, and IA-2 were measured in the first sample, and HLA class II typing was performed. RESULTS: Of 147 family members with ICA &amp;gt; or = 20 JDF U on at least one occasion, 29 developed type 1 diabetes after a median of 3.2 years (maximum 18.1). The cumulative risk of developing diabetes within 15 years was 47% (95% CI 28-67) for all family members with ICA &amp;gt; or = 20 JDF U, 2.8% (0-8.2) for those with ICA alone, and 66% (44-87) for those with at least one additional autoantibody marker. There were no differences in age, HLA class II type, or levels of ICA, insulin autoantibodies, or IA-2 antibodies between those who developed diabetes within 5 years of testing and those who developed diabetes after this time. GAD antibody levels we ..., however, higher in those who progressed more slowly. CONCLUSIONS: Family members with ICA alone are at low risk of progression to diabetes. Rapid development of disease after ICA detection could not be distinguished from delayed development on the basis of autoantibodies or markers of genetic susceptibility, and those with multiple antibodies remained at high risk throughout long-term follow-up. This suggests that all family members with multiple islet autoantibodies are destined to develop autoimmune diabetes.
11C-Acetate can be Used in Place of 18F-Fluorodeoxyglucose for Positron Emission Tomography Imaging of Non-small Cell Lung Cancer with Higher Sensitivity for Well-Differentiated Adenocarcinoma
Authors: Hiroaki Nomori, Hidekatsu Shibata, Kimiichi Uno, Kenichi Iyama, Yumi Honda, Rumi Nakashima, Kazuya Sakaguchi, Tomoyuki Goya, Iwao Takanami, Kiyoshi Koizumi, Takashi Suzuki, Masahiro Kaji, Hirotoshi Horio
Journal: Journal of Thoracic Oncology (2008)
Bryan John Hockey
Authors: A. H. Sarafian
Journal: BMJ (2011)

Bryan John Hockey was born on 10 August 1926 in Radstock, Somerset. He obtained a scholarship to Selwyn College, Cambridge, to study medicine. He achieved a first in natural sciences and then did his clinical studies at University College Hospital, London, qualifying in 1949. He did house jobs in Guildford and then two years of national service in the Royal …