tbuckley/cabot-search huggingface dataset:
Abstract 1786: Development and pharmacological properties of PEGylated glucuronide-auristatin linkers
Authors: Patrick J. Burke, Joseph Z. Hamilton, Joshua H. Hunter, Scott C. Jeffrey, Svetlana O. Doronina, Nicole M. Okeley, David W. Meyer, Peter D. Senter, Robert P. Lyon
Journal: Cancer Research (2014)

Abstract Antibody-drug conjugates (ADCs) are an emerging therapeutic modality for the treatment of cancer, exemplified by the recent clinical success of brentuximab vedotin and ado-trastuzumab emtansine. The majority of ADCs currently in development include functionalities that are hydrophobic, resulting in increased plasma clearance. Consequently, there has been significant interest in generating new linkers that compensate for this potential liability. In an attempt to mitigate the pharmacokinetic impact of monomethylauristatin E (MMAE) when conjugated to an antibody, we prepared drug-linkers incorporating a polyethylene glycol (PEG) polymer. Initial work demonstrated that incorporation of a discrete PEG24 polymer into the cleavable β-glucuronide-MMAE linker system could either increase or decrease the plasma clearance of the resulting ADCs, depending upon the configuration of the PEG. When inserted into the drug-linker as a stretcher unit between the maleimide and the cleavage site, PEG24 elicited increased ADC plasma clearance. Conversely, incorporation of the PEG24 as a side chain from a modified lysine residue adjacent to the maleimide resulted in ADCs with slower clearance. These differences in ADC pharmacokinetics translated into corresponding differences in antitumor activity in two xenograft models. Thus, incorporation of PEG24 into ADC linkers impacts both pharmacokinetics and activity in a structure-dependent manner. Citation Format: Patrick J. Burke, Joseph Z. Hamilton, Joshua H. Hunter, Scott C. Jeffrey, Svetlana O. Doronina, Nicole M. Okeley, David W. Meyer, Peter D. Senter, Robert P. Lyon. Development and pharmacological properties of PEGylated glucuronide-auristatin linkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1786. doi:10.1158/1538-7445.AM2014-1786
Abstract 75: Ventricular Fibrillation in Cardiac Arrest with Nonshockable Initial Rhythm
Authors: Fernando Rosell-Ortiz, Francisco J Mellado-Vergel, Patricia Fernández-Valle, Auxiliadora Caballero-García, Ismael González-Lobato, Santiago Vergara-Pérez, María M Ruiz-Montero, Manuela Martínez-Lara, Itziar Vivar-Díaz, Javier García del águila
Journal: Circulation (2014)

The initial shockable rhythm in cardiac arrest is a well known factor of good prognosis. Little is known about the influence of the onset of ventricular fibrillation during resuscitation at cardiac arrest whose initial rhythm was non-shockable. Methods: Retrospective analysis of a continuous registry of out-of-hospital cardiac arrest (OHCA) Inclusion criteria, all consecutive patients suffering OHCA attended by emergency teams in Andalusia, Spain. Period January 2008 - December 2012. Results: 5067 patients were included. According to the initial cardiac arrest rhythm 1038 (20.5%) cases presented initial shockable rhythm (SR) and 4029 (79.5%) with non-shockable initial rhythm (NSR). Of these patients 150 (3%) reported one or more episodes of ventricular fibrillation during resuscitation (NSRVF). The main clinical characteristics of these three groups are shown in Table 1. Variables associated with good neurological status at hospital discharge are shown in Table 2. Conclusions: NSRVF patients present higher survival with good neurological status than NSR patients. These patients may represent a third prognostic group in cardiac arrest with a survival rate between shockable and non-shockable initial rhythms. Table 1. Clinical data of patients regarding rhythm of cardiac arrest Table 2. Variables associated with good neurological status at discharge (CPC 1-2 ) SD: Standard deviation. IQR: Interquartile range. OR: Odds Ratio. CI: Confidence Interval. ET: Emergency Team. VF: Ventricular Fibrillation. CPR: Cardiopulmonary resuscitation. CPC: Cerebral Perfomance Category. ROSC: Return of spontaneous circulation
Abstract IA22: Innate immune cell PI3K gamma as a target for suppression of pancreatic ductal adenocarcinoma
Authors: Megan Kaneda, Chanae Hardamon, Michael C. Schmid, Michael Bouvet, Franco Novelli, Emilio Hirsch, Andrew Lowy, Judith A. Varner
Journal: Cancer Research (2015)

Abstract Ductal adenocarcinoma of the pancreas (PDAC) is a devastating disease that will afflict greater than 40,000 Americans. Less than 5% of these new pancreatic cancer patients will survive 5 years following diagnosis. PDAC is rarely detected in the early stages, with more than 80% of patients presenting with locally unresectable or metastatic disease at the time of diagnosis. As this form of cancer is also resistant to current cytotoxic therapies and ionizing radiation, novel therapeutic and diagnostic approaches are desperately needed to improve patient outcome. A characteristic feature of PDAC is the presence of an abundant, inflammatory infiltrate. In response to tumor-derived chemoattractants, we found that myeloid cells invade tumors where they promote immunosuppression, resulting in tumor growth and metastasis. We discovered that myeloid cell PI3-kinase gamma (PI3Kgamma) controls tumor immunosuppression, as PI3Kgamma signaling inhibits pro-inflammatory gene expression responses in macrophages, monocytes and granulocytes and promotes anti-inflammatory responses. Suppression of PI3Kgamma in mutant mice and in mice treated with pharmacologic inhibitors of PI3Kgamma promotes CD8+ T cell anti-tumor immune responses, leading to a 50% reduction in tumor growth and metastasis in orthotopic mouse models of pancreatic carcinoma and significant extension of survival in GEM models of PDAC (PDX1-cre; LSL-KrasG12D/+; LSL-Trp53 R172H/+). Furthermore, PI3Kgamma inhibition blocks macrophage stimulation of collagen deposition by fibroblasts in PDAC. We are exploring the combination of PI3kinase gamma inhibition with tumor cell and T cell targeted therapeutics could significantly reduce tumor growth and metastasis of PDAC. These approaches could improve patient outcomes by reducing tumor progression and preserving organ function by inhibiting desmoplasia. Citation Format: Megan Kaneda, Chanae Hardamon, Michael C. Schmid, Michael Bouvet, Franco Novelli, Emilio Hirsch, Andrew Lowy, Judith A. Varner. Innate immune cell PI3K gamma as a target for suppression of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr IA22.
Abstract 12536: Lower Thromboembolic and Bleeding Events With Uninterrupted Warfarin Compared to Interrupted Warfarin and Heparin Bridging in Atrial Fibrillation Ablation. Evidence From a Meta-Analysis
Authors: Ramez Nairooz, Partha Sardar, Saurav Chatterjee, Wilbert S Aronow, Kenneth L Gould
Journal: Circulation (2014)

Introduction: Optimal anticoagulation strategy in patients undergoing atrial fibrillation ablation (AFA) is controversial. Trials comparing uninterrupted warfarin (UW) with interrupted warfarin and heparin bridging (IW) peri-procedural in AFA are inconsistent in showing decreased thromboembolic and bleeding events with UW. We sought to perform a meta-analysis comparing both strategies in AFA. Methods: We searched online databases till May 2014 for case-control studies that compared patients undergoing AFA with UW versus IW. Studies without a control arm, and those that included patients not on anticoagulation peri-procedural were excluded. We used odds ratio and random effects model. When event rates were less than 1% we used Peto Odds ratio. We explored the hypothesis that UW decreased thromboembolic events with equal bleeding rates compared to IW therapy in patients undergoing AFA. Results: Our search yielded 13 observational and 1 randomized trial. A total of 17628 patients were included, of those 7964 on UW vs 9664 on IW. Patients on UW had lower combined Stroke and TIA compared with IW (Odds ratio (OR) 0.29, 95% confidence interval (CI) [0.12, 0.72]; p=0.007). Consistently Stroke were lower with UW (Peto OR 0.21, 95% CI [0.13, 0.33]; p&lt;0.0001) and TIA (Peto OR 0.25, 95% CI [0.13, 0.51]; p=0.0001). Major bleeding events were also lower with UW (OR 0.73, 95% CI [0.57, 0.94]; p=0.02) as well as minor bleeding (OR 0.36, 95% CI [0.23, 0.56]; p&lt;0.0001) compared to IW. Cardiac tamponade were equal with both strategies (POR 0.84, 95% CI [0.61, 1.16]; p=0.3). Conclusion: In AFA, UW decreases the incidence of stroke and TIA with lower major and minor bleeding events compared to IW. These results recommend use of UW rather than IW strategy in AFA.
Incidence of Leukemia and Other Tumors in Thymectomized Irradiated Mice Bearing Thymic Transplants&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Roger W. O'Gara, Jewel Ards
Journal: JNCI Journal of the National Cancer Institute (1961)

The effect of transplants of thymic tissue from newborn mice on the incidence of radiation-induced leukemia was investigated in strain C57BL mice. Thymectomized irradiated mice either were given an intrasplenic or a subcutaneous transplant of neonatal thymic tissue or were subjected to a sham intrasplenic transplantation. Mice bearing an intrasplenic transplant of thymic tissue and those given a sham intrasplenic transplant had essentially the same incidence of leukemia (10.5 and 8.7%, respectively). Mice bearing subcutaneous transplants of thymic tissue had a higher incidence of leukemia (31.6%) though not as high as the irradiated, nonthymectomized control animals (63.6%). The thymic implants were identified in the spleens of 34 percent of the animals examined during the 14-month observation period after transplantation. Histologic study of early and late implants showed normal growth and development of the thymic tissue in the spleens of irradiated mice. An apparent increase in the incidence of epithelial tumors in thymectomized X-irradiated mice is discussed briefly.
Abstract 4369: The microRNA-218-survivin axis regulates cervical cancer cell migration and invasion
Authors: Ryunosuke Kogo, Christine How, Jeff Bruce, Willa Shi, Kenneth W. Yip, Laurie Ailles, Fei-Fei Liu
Journal: Cancer Research (2014)

Abstract MicroRNA (miR)-218 down-regulation has been reported in numerous human malignancies. In cervical cancer, we identified that lower miR-218 expression was significantly associated with poorer overall survival, disease-free survival, and pelvic/para-aortic lymph node recurrence. Further analyses of cervical cancer data from The Cancer Genome Atlas (TCGA) identified that this down-regulation was associated with a genomic locus loss (hsa-mir-218-1:4p15.31, hsa-mir-218-2:5q34, n=105). The objective of the current study was to elucidate the cellular and molecular functions of miR-218. MiR-218 transfection into cervical cancer cells (SiHa and ME-180) significantly reduced cell migration (by 66% and 89%, respectively), invasion (by 49% and 67%, respectively), and clonogenic capacity (by 42% and 53%, respectively), relative to control-transfected cells (P&amp;lt;0.05). In order to identify clinically relevant miR-218 target genes, we used an integrated trimodal approach, incorporating DNA microarray (Affymetrix Human Genome U133 Plus 2.0) analyses of 79 clinical samples, miR-218 transfection, and miRDB target prediction. The most significant target was survivin (BIRC5); miR-218 transfection confirmed a reduction in survivin mRNA and protein expression in both SiHa and ME-180 cells. Furthermore, a direct interaction between the survivin-3′UTR and miR-218 was validated using a luciferase reporter assay. siRNA knockdown of survivin in SiHa and ME-180 significantly reduced cell migration (by 76% and 83%, respectively), invasion (by 79% and 88%, respectively), and clonogenic capacity (by 98% and 97%, respectively), relative to control cells (P&amp;lt;0.05). YM155, a small-molecule survivin suppressant, effectively reduced survivin mRNA and protein levels in a concentration- and time-dependent manner. This compound correspondingly decreased cervical cancer cell proliferation and clonogenic survival. Our results suggest that the miR-218-survivin axis plays an important role in cervical cancer progression. Citation Format: Ryunosuke Kogo, Christine How, Jeff Bruce, Willa Shi, Kenneth W. Yip, Laurie Ailles, Fei-Fei Liu. The microRNA-218-survivin axis regulates cervical cancer cell migration and invasion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4369. doi:10.1158/1538-7445.AM2014-4369
When I use a word ...: That's show business
Authors: J. Aronson
Journal: BMJ (1999)

Compared with many drugs, the product development of a new contraceptive is expensive and relatively high risk.It is unlikely that the pattern of contraceptive use will change radically in the next 10 years.No one method will be suitable for everyone, and individuals' preferences will probably change through their reproductive life.In the next five years more sophisticated systems for the delivery of steroid hormones, through or under the skin and into the uterus, will extend the range of options available.In five to 10 years new steroid antagonists such as antiprogestins will replace some current contraceptive methods, such as gestogen only pills, and probably lead to new approaches like a "once a month" pill.By 10-15 years, the dream of an effective safe male pill will probably become a reality, shifting the burden of responsibility for contraception more equally between men and women.Only then will women have truly achieved "the fifth freedom"-freedom from the burden of excessive fertility. 20
Abstract 15628: Physically Active Women With Type 1 Diabetes Have Improved Hyperglycemia but Not Overall Glycemic Control
Authors: Lindsey M Duca, Talia Brown, Sandra Ruland, Rachel Sippl, Janet Snell-Bergeon
Journal: Circulation (2014)

Cardiovascular disease (CVD) is the main cause of mortality in type 1 diabetes (T1D) patients. Chronic hyperglycemia has been linked to progression of coronary artery calcification and CVD events. Physical activity (PA) may improve hyperglycemia in T1D patients. The objective of this study was to analyze the relationship between PA and glucose parameters obtained from Continuous Glucose Monitoring (CGM).  This study included 43 women with T1D who were 33±9 (mean±SD) years of age from the Women, Insulin and Sex Hormones study. Subjects wore a CGM (Dexcom SEVEN PLUS) for an average of 14±12 days. Glycemic control was evaluated by the average mean glucose, percentage of values within target range (70-180mg/dL), hypoglycemic ( 180mg/dL), and hemoglobin A1c (HbA1c). Participants were classified into two categories, met (n=8) or did not meet (n=34) the AHA guidelines for moderate PA of at least 150 minutes or vigorous PA of at least 60 minutes per week.  T1D women who met the PA guidelines had a lower percent of time hyperglycemic and a higher percent of time in the target range, and a smaller standard deviation in the mean glucose (table). There was no difference in HbA1c. In multivariable analysis, the percent of time hyperglycemic was associated with central mean arterial pressure, systolic pressure, and diastolic pressure (p=0.02) when adjusting for age, race, and minutes of PA per week. The percent of time in target was associated with central mean pressure, systolic pressure, and diastolic pressure (p=0.02) adjusting for the same variables.  Despite no difference in overall glycemic control measured by HbA1c, physically active T1D women had less hyperglycemia and spent more time in the target range compared to sedentary women. These were both associated with measures of central arterial stiffness. Therefore, PA may decrease the risk for CVD through specific effects on reduced overnight glucose and variability, not overall glycemic control alone.
Endocrine function and bone disease during long‐term chelation therapy with deferasirox in patients with β‐thalassemia major
Authors: Maddalena Casale, Serena Citarella, Aldo Filosa, Elisa De Michele, Francesco Palmieri, Alfonso Ragozzino, Giovanni Amendola, Umberto Pugliese, Immacolata Tartaglione, Filomena Della Rocca, Patrizia Cinque, Bruno Nobili, Silverio Perrotta
Journal: American Journal of Hematology (2014)

Iron overload in β-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n = 5) and hypoparathyroidism (n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased (P = 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre-exisisting was observed in a real clinical practice setting.
TOXIC REACTIONS ACCOMPANYING SECOND COURSES OF SULFONAMIDES IN PATIENTS DEVELOPING TOXIC REACTIONS DURING A PREVIOUS COURSE
Authors: Harry F. Dowling, Harold L. Hirsh, Mark H. Lepper
Journal: Annals of Internal Medicine (1946)

Article1 April 1946TOXIC REACTIONS ACCOMPANYING SECOND COURSES OF SULFONAMIDES IN PATIENTS DEVELOPING TOXIC REACTIONS DURING A PREVIOUS COURSEHARRY F. DOWLING, M.D., F.A.C.P., HAROLD L. HIRSH, M.D., MARK H. LEPPERHARRY F. DOWLING, M.D., F.A.C.P.Search for more papers by this author, HAROLD L. HIRSH, M.D.Search for more papers by this author, MARK H. LEPPERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-24-4-629 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe sulfonamide drugs are so commonly administered at the present time that practically every person has received one of them on some occasion. Consequently, it is of importance to consider what will happen when these individuals receive sulfonamides a second time. Lyons and Balberor1reported that in patients who received a course of sulfathiazole without exhibiting any toxic effects "drug fever" was more likely to develop during a second course of sulfathiazole than in patients receiving an initial course of this drug. Two of us2have shown that this principle also holds for other sulfonamides, and, furthermore, that when patients...Bibliography1. LYONSBALBEROR RHH: Febrile reactions accompanying the readministration of sulfathiazole, Jr. Am. Med. Assoc., 1942, cxviii, 955-958. CrossrefGoogle Scholar2. DOWLINGLEPPER HFMH: "Drug fever" accompanying second courses of sulfathiazole, sulfadiazine and sulfapyridine, Am. Jr. Med. Sci., 1944, ccvii, 349-353. CrossrefGoogle Scholar3. PARK RG: Sulphonamide allergy, Brit. Med. Jr., 1944, i, 781-782. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication August 2, 1945.From the George Washington Medical Division, Gallinger Municipal Hospital and the Department of Medicine, George Washington University.†Capt. Lepper's contribution to this study was made before he entered military service. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug-Protein Conjugation and its Immunological ConsequencesImmunization of mice against barbiturates and the effect on the disposition of [3H]phenobarbitalThe SulfonamidesProlonged Treatment of Urinary-Tract Infections with SulfamethoxypyridazineCLINICAL TOXICITY OF SULFONAMIDESSulfonamideStatistical analysis of 242 cases of meningococcus meningitisDrug allergy 1 April 1946Volume 24, Issue 4Page: 629-633KeywordsArmed forcesDrugsFeversHospital medicineSulfonamide ePublished: 1 December 2008 Issue Published: 1 April 1946 PDF downloadLoading ...
Multidisciplinary Proactive Psychiatric Consultation Service: Impact on Length of Stay for Medical Inpatients
Authors: William H. Sledge, Ralitza Gueorguieva, Paul Desan, Janis E. Bozzo, Julianne Dorset, Hochang Benjamin Lee
Journal: Psychotherapy and Psychosomatics (2015)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Mental illness correlates with an increased length of stay (LOS) for patients hospitalized for medical conditions. While psychiatric consultations help manage mental illness among those hospitalized for medical conditions, consultations initiated by nonpsychiatric mental disease may lack maximum effectiveness. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In a before-and-after design, in 2 contiguous years LOS for internist-initiated, conventional consultation (CC) as usual treatment was compared to LOS of a proactive, mental health professional-initiated, multidisciplinary intervention delivered by the behavioral intervention team (BIT) on the same units. The patient populations included general medical patients with a variety of illnesses. Patients were treated in 3 different inpatient settings with a total capacity of 92 beds serving 15,858 patient visits over 3 comparison years. BIT comprised a psychiatrist, a nurse, and a social worker, each of whom performed the specific tasks of their professional discipline, while collaborating among themselves and their health-care colleagues. BIT provided timely, appropriate, and effective patient care alongside consultative advice and education to their corresponding professional peers. BIT was compared to CC on the outcome of LOS. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; There was a statistically significant reduction of LOS favoring BIT over CC for patients with an LOS of &lt;31 days which persisted while controlling for multiple co-morbid factors. Also, a statistically significant spillover effect was suggested by the overall improvement of LOS on units implementing BIT. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; BIT is a promising means of lowering LOS on general medical units while providing a high level of care and staff support.
Patients hospitalized with 2009 pandemic influenza A (H1N1) - New York City, May 2009.
Authors: M. E. Slopen, M. C. Mosquera, S. Balter, B. D. Kerker, M. A. Marx, M. R. Pfeiffer, A. Fine, J. Eavey, T. G. Harris, E. C. Olson, C. Stayton, C. Wu, E. H. Lee
Journal: MMWR Morbidity and Mortality Weekly Report (2009)