tbuckley/cabot-search huggingface dataset:
Abstract 1227: Macrophage depletion enhances the anticancer efficacy of eribulin mesylate in mice bearing syngeneic tumors.
Authors: Diana I. Albu, Bruce A. Littlefield, Mary Woodall-Jappe
Journal: Cancer Research (2013)

Abstract Recent reports utilizing the MMTV-PyMT spontaneous model of breast cancer established that inhibition of macrophage recruitment to the tumors resulted in increased anti-cancer activity of paclitaxel. Eribulin mesylate (Halaven®) is a non-taxane microtubule-dynamics inhibitor recently approved for third line clinical use in patients with heavily pretreated metastatic breast cancer, based upon a statistically significant increase in median overall survival (OS) compared to treatment of physician's choice. In the present study we investigated whether systemic depletion of macrophages would enhance eribulin anti-tumor efficacy. In the subcutaneous Lewis lung carcinoma (LLC) syngeneic murine tumor model, we found that macrophage depletion via liposomal clodronate enhanced eribulin inhibition of tumor growth. Current studies are investigating the mechanism(s) of this activity. Citation Format: Diana I. Albu, Bruce A. Littlefield, Mary Woodall-Jappe. Macrophage depletion enhances the anticancer efficacy of eribulin mesylate in mice bearing syngeneic tumors. [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 1227. doi:10.1158/1538-7445.AM2013-1227
Transient Decrease in I-131 and Tc-99m Thyroid Uptake After Neck Trauma
Authors: RUTH HARDOFF, ELHANAN GREENBERG, ELIZABETH BARON, MAXIM SHEINFELD
Journal: Clinical Nuclear Medicine (1989)

Hemorrhage into the thyroid gland secondary to trauma is uncommon. It is postulated that its mechansim involves the rupture of small veins within the thyroid. It has been described as a cause of respiratory distress and dysphagia. The authors report the case of a patient who after neck trauma, developed a reduction of I-131 and Tc-99m pertechnetate uptake followed by subclinical borderline hypothyroidism.
Antiadhesive properties of biological surfaces are protective against stimulated granulocytes.
Authors: J Fehr, R Moser, D Leppert, P Groscurth
Journal: Journal of Clinical Investigation (1985)

Despite the fact that a series of endogenous and exogenous inflammatory mediators are potent activators of circulating granulocytes, damage of vascular endothelium, a primary target tissue, is a rather unusual event in systemic inflammatory states. Since mediator-induced neutrophil hyperadhesiveness on plastic tissue culture dishes is invariably accompanied by intense release of lysosomal granule constituents and respiratory burst activation, thus representing a powerful model to investigate neutrophil cytotoxic states, comparative studies with neutrophils suspended in autologous plasma in the presence or absence of N-formyl-Met-Leu-Phe (2.5 microM), the most potent adhesion inducer, were performed on different biologic surfaces. On optimally adherent closed monolayers of cultured endothelial cells or fibroblasts we observed poor stimulation of adhesion as well as minimal granule release and hexose monophosphate pathway activation. Functional behavior of neutrophils on single molecular components of basal laminas such as fibronectin and collagen (type IV) coats was intermediate, with positive adhesion promotion but markedly reduced metabolic activation. When tested on endothelial cell-derived extracellular matrices, neutrophils again showed functional nonresponsiveness to N-formyl-Met-Leu-Phe. Scanning electron microscopy revealed an impressive congruency between the degree of cellular spreading and metabolic activation in the presence of N-formyl-Met-Leu-Phe, with maximally flattened neutrophils on plastic vs. nonspread, polarized cells on monolayers. Identical results were obtained by using other adhesion inducers such as complement-activated plasma or endotoxin. Lack of cell injury by N-formyl-Met-Leu-Phe-exposed neutrophils was corroborated by the absence of tracer release from [111In]tropolonate-labeled endothelium. These results indicate that biologic surfaces possess antiadhesive properties that protect them from cytotoxic damage by stimulated angry phagocytes.
Metricating Medicine: How Fast, How Far?
Authors: Edward J. Huth
Journal: New England Journal of Medicine (1974)

The conclusions of the United States Metric Study on the "advantages and disadvantages of increased use of the metric system in the United States"1 could have been predicted even before it was authorized by the Congress in 1968. Every nation with ambitions in science must now train its scientists to read and write English; every nation that needs international trade must now use the metric system. Our exporting corporations know where their bread is buttered, and this is why they are now leading in the inevitable conversion to metric units in our commerce and technology.Metric units are not strangers . . .
Mortality Risk Reduction Associated With Smoking Cessation in Patients With Coronary Heart Disease
Authors: Julia A. Critchley, Simon Capewell
Journal: JAMA (2003)

<h3>Context</h3> As more interventions become available for the treatment of coronary heart disease (CHD), policy makers and health practitioners need to understand the benefits of each intervention, to better determine where to focus resources. This is particularly true when a patient with CHD quits smoking. <h3>Objective</h3> To conduct a systematic review to determine the magnitude of risk reduction achieved by smoking cessation in patients with CHD. <h3>Data Sources</h3> Nine electronic databases were searched from start of database to April 2003, supplemented by cross-checking references, contact with experts, and with large international cohort studies (identified by the Prospective Studies Collaboration). <h3>Study Selection</h3> Prospective cohort studies of patients who were diagnosed with CHD were included if they reported all-cause mortality and had at least 2 years of follow-up. Smoking status had to be measured after CHD diagnosis to ascertain quitting. <h3>Data Extraction</h3> Two reviewers independently assessed studies to determine eligibility, quality assessment of studies, and results, and independently carried out data extraction using a prepiloted, standardized form. <h3>Data Synthesis</h3> From the literature search, 665 publications were screened and 20 studies were included. Results showed a 36% reduction in crude relative risk (RR) of mortality for patients with CHD who quit compared with those who continued smoking (RR, 0.64; 95% confidence interval [CI], 0.58-0.71). Results from individual studies did not vary greatly despite many differences in patient characteristics, such as age, sex, type of CHD, and the years in which studies took place. Adjusted risk estimates did not differ substantially from crude estimates. Many studies did not adequately address quality issues, such as control of confounding, and misclassification of smoking status. However, restriction to 6 higher-quality studies had little effect on the estimate (RR, 0.71; 95% CI, 0.65-0.77). Few studies included large numbers of elderly persons, women, ethnic minorities, or patients from developing countries. <h3>Conclusions</h3> Quitting smoking is associated with a substantial reduction in risk of all-cause mortality among patients with CHD. This risk reduction appears to be consistent regardless of age, sex, index cardiac event, country, and year of study commencement.
Disseminated Aspergillosis and Moniliasis Associated with Agranulocytosis and Antibiotic Therapy
Authors: N. E. Rankin
Journal: BMJ (1953)

GOLD THERAPY IN RHEUMATOID ARTHRITIS arsenic had been selected in that they were all early and frankly active cases with an E.S.R. of over 40 mm. in one hour.The remaining groups included patients over 50 years of age and with advanced disease.Table II shows the results adjusted by the removal of such patients from each group.The figures in this small series indicate that the results of a single course of treatment with gold salts are no better than those obtained by the other methods described.TABLE II.-Results Adjusted to Exclude Elderly and Inactive Cases Treat-No.At End of Course At 3 Months At 1 Year m e t of ment Cases A B A B A B Gold .. 38 (0) 75 50 62 28 53 30 Copper 40 (20) 77 52 66 32 50 33Saline . .
Nitroprusside Therapy for a Patient With a Pheochromocytoma
Authors: Ace Lipson
Journal: JAMA (1978)

WE DESCRIBE a patient in hypertensive crisis from a pheochromocytoma, in whom sodium nitroprusside was used without adrenergic blockers, and subsequently was administered for a one-week period in conjunction with blockers to achieve preoperative and ultimately intraoperative blood pressure control. We believe this represents the most extensive experience with this drug in one patient with this condition.  Report of a Case  A 32-year-old woman was transferred to the George Washington University Hospital Intensive Care Unit from another hospital, with uncontrolled hypertension six hours after cesarean section. The patient had a history of labile hypertension and diet-controlled diabetes. She was hypertensive during her first pregnancy, miscarrying at six months.  During the current pregnancy, blood pressure became 140/90 mm Hg, and occasional flushing, pedal edema, and proteinuria occurred. At 32 weeks, she was admitted with a blood pressure of 220/140 mm Hg, unchanged by diazepam and bed rest. Despite methyldopa therapy, 500
Cytotoxic Drugs in Treatment of Nonmalignant Diseases
Authors: ALFRED D. STEINBERG
Journal: Annals of Internal Medicine (1972)

The basis for using cytotoxic drugs in inflammatory diseases of uncertain cause is their immunosuppressive properties. These drugs interrupt nucleic acid and protein synthesis, thereby inhibiting various immune responses at different stages. Specific inhibition of an immune response is possible through drug-induced tolerance. Many of the agents have anti-inflammatory properties that may be a major factor in their efficacy. In short-term controlled trials, both cyclophosphamide and azathioprine have been useful in treatment of rheumatoid arthritis and systemic lupus erythematosus, cyclophosphamide in nephrosis, and methotrexate and azathioprine in psoriasis and psoriatic arthritis. Azathioprine was ineffective in iridocyclitis, nephritis, nephrosis, Crohn's disease, chronic hepatitis, and asthma. Cytotoxic drugs may increase the risk of infection, predispose to malignancy, and increase mutations in offspring. Specific side effects include hemorrhagic cystitis from cyclophosphamide, cirrhosis from methotrexate, and altered germ cell production by alkylating agents. Only long-term controlled trials, not uncontrolled reports or positive short-term controlled trials, will justify widespread clinical use of these drugs in inflammatory diseases.
Epithelial Ovarian Cancer
Authors: Robert J. Morgan, Ronald D. Alvarez, Deborah K. Armstrong, Barry Boston, Robert A. Burger, Lee-may Chen, Larry Copeland, Marta Ann Crispens, David Gershenson, Heidi J. Gray, Perry W. Grigsby, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Ursula A. Matulonis, David M. O'Malley, Richard T. Penson, Steven W. Remmenga, Paul Sabbatini, Russell J. Schilder, Julian C. Schink, Nelson Teng, Theresa L. Werner
Journal: Journal of the National Comprehensive Cancer Network (2011)

Chapter Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 Primary Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 Early-Stage Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 Advanced-Stage Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 Neoadjuvant Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 Intraperitoneal Chemotherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 Consolidation Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 Therapeutic Strategies for Recurrent Ovarian Cancer . . . . . . . . . . . . . 196 Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 Salvage Chemotherapy for Platinum-Sensitive Disease. . . . . . . . . . 197 Salvage Chemotherapy for Platinum-Refractory or Platinum-Resistant Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 Hormonal Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 High-Dose Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 Key Practice Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 Suggested Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
View from English pilot site of Safer Patients Initiative
Authors: S. Ramsden
Journal: BMJ (2011)

I was the chief executive officer of Luton and Dunstable Hospital, the pilot site in England for the Safer Patients Initiative, 2004-8 (SPI1). The main objective of SPI1 was to reduce adverse events (as measured by the global trigger tool) by half. We achieved this, as well as a reduction of 55% in cardiac arrests, the main reason why our hospital standardised mortality ratio fell from being …
Clinical judgment in the diagnosis and management of frequency and dysuria in general practice.
Authors: T C O'Dowd, J E Smail, R R West
Journal: BMJ (1984)

In a study of 40 women with the urethral syndrome and 46 women with conventional urinary tract infection, none of whom was pregnant, general practitioners predicted the diagnosis correctly before the report on the midstream urine specimen was received, as evidenced by their management. They seemed to do this by balancing the symptom of dysuria with the psychological make up of the patient: patients with the urethral syndrome suffered appreciably less dysuria than patients with urinary tract infection; patients with the urethral syndrome suffered appreciably more psychological illness. This ability to distinguish between the two disorders has important clinical and economic implications.
A noninflammatory pathway for pregnancy loss: innate immune activation?
Authors: Jane E. Salmon
Journal: Journal of Clinical Investigation (2004)

Although the mechanisms of immune-mediated pregnancy loss are unknown, investigations are currently focused on mediators of immune activation and tissue injury at the maternal-fetal interface. A new study, however, demonstrates that systemic inflammatory mediators can induce pregnancy failure in a different way, by inhibiting ovarian hormone production, and identifies links between the immune and reproductive endocrine systems.
Expression of IAP-family proteins in adult acute mixed lineage leukemia (AMLL)
Authors: Yasunori Nakagawa, Maki Hasegawa, Morito Kurata, Kouhei Yamamoto, Shinya Abe, Miori Inoue, Tamiko Takemura, Katsuiku Hirokawa, Kenshi Suzuki, Masanobu Kitagawa
Journal: American Journal of Hematology (2005)

Inhibitor of apoptosis protein (IAP)-family proteins suppress apoptotic signaling in normal/neoplastic cells in various settings. To determine the apoptosis-resistant mechanism in adult acute mixed lineage leukemia (AMLL) with biphenotypic blasts responsible for resistance against chemotherapy, the expression levels of IAP-family proteins in AMLL bone marrow cells were analyzed by quantitative RT-PCR. The overall expression levels of IAPs were higher than those in control, AML, and ALL cells. A significant difference for the expression of survivin was observed between AMLL and AML (P < 0.05), and differences between AMLL and ALL were significant for the expression of survivin (P < 0.05), NAIP (P < 0.05), and XIAP (P < 0.05). These findings suggest that higher expression of various IAPs is associated with the chemotherapy-resistant nature of this specific type of leukemia. Am. J. Hematol. 78:173–180, 2005. © 2005 Wiley-Liss, Inc.
Abstract 4421: PDE5 inhibitors suppress proliferation and augment the epithelial barrier by activating PKG2 in the colon
Authors: Rui Wang, In-Kiu Kwon, Sridhar Subbaramia, Darren D. Browning
Journal: Cancer Research (2012)

Abstract Increasing cGMP levels has emerged as a potentially important suppressor of tumorigenesis in the colon, but the downstream signaling is poorly defined and a viable therapeutic strategy remains to be established. The present study has tested whether type 2 cGMP-dependent protein kinase (PKG2) mediates the homeostatic effects of cGMP in the colon. In addition, the feasibility of using phosphodiesterase 5 (PDE5) inhibitors therapeutically to increase cGMP levels in the colon mucosa has been examined. PKG2 is a central effector of cGMP in enterocytes, and consistent with a growth-inhibitory and differentiation-promoting role, knockout animals showed crypt hyperplasia and reduced mature goblet cells in the colonic mucosa. This phenotype is similar to guanylyl-cyclase C (GCC) knockout animals, which have also been reported to exhibit increased susceptibility to colon tumorigenesis. The possibility that PKG2 signaling might be activated pharmacologically, was examined using PDE5 inhibitors to regulate colonic proliferation and differentiation. These experiments demonstrated that intraperitoneal administration of clinically relevant PDE5 inhibitors provoked a rapid increase cGMP levels in the colon mucosa of mice. Moreover, prolonged treatment with PDE5 inhibitors led to reduced proliferation in the colonic crypts and a dramatic increase in mature goblet cells. Consistent with the importance of PKG2 in this process, the PDE5 inhibitors did not inhibit proliferation or increase goblet cell numbers in PKG2 knockout animals. The increase in goblet cell density in PDE5 inhibitor-treated animals was striking (50%, 85%, and 44% relative to controls in the ascending, transverse and descending colon respectively). Reduced basal epithelial apoptosis measured in PDE5 inhibitor treated animals suggested the the increased goblet cells could have a barrier-protective effect. To test this possibility further, the effect of PDE5 inhibitor treatment on epithelial damage by dextran sulfate sodium was measured. These studies demonstrated a significant attenuation of disease activity by PDE5 inhibitor treatment in this colitis model. In summary, our results demonstrate a central role for PKG2 in the regulation of proliferation and differentiation in the colon mucosa. In addition, this pathway can be exploited using PDE5 inhibitors, suggesting that these agents could be part of a novel therapeutic strategy for colon cancer prevention. 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 4421. doi:1538-7445.AM2012-4421
Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response
Authors: Michael Keeney, Heather Waters, Katherine Barcay, Xinyi Jiang, Zhenyu Yao, Jukka Pajarinen, Kensuke Egashira, Stuart B. Goodman, Fan Yang
Journal: Biomaterials (2013)
The chronically instrumental ewe: a model for studying vascular reactivity to angiotensin II in pregnancy.
Authors: C R Rosenfeld, N F Gant
Journal: Journal of Clinical Investigation (1981)

Vascular refractoriness to the systemic pressor effects of angiotension II (AII) develops normally during human pregnancy. To ascertain if the ewe might provide a suitable animal model to study the mechanisms responsible for this response (unique to pregnancy) we studied this phenomenon in unanesthetized, chronically instrumented nonpregnant and pregnant sheep, 68-143 d gestation. In these studies dose-response curves were established for changes in both mean arterial pressure and uterine blood flow. The pressor response to continuous infusions of AII increases as a function of the dose of AII in both nonpregnant and pregnant animals (P less than 0.001), R = 0.943 and 0.879, respectively. However, the pregnant animals were refractory to the pressor effects of AII, requiring 0.016 microgram of AII/min per kg to elicit a 20 mm HG rise in mean arterial pressure, in contrast to 0.009 for nonpregnant animals. The slope and intercept for the regression lines are different at P less than 0.001. In pregnant animals the dose-response curve for uterine blood flow was also determined. Increases in uterine blood flow were observed at doses of AII less than 0.016 microgram/min per kg, while larger doses resulted in a progressively greater reduction in blood flow. It appears likely that the ewe may serve as an animal model suitable for the further study of the unique pregnancy-modified systemic and uteroplacental vascular responses elicited by AII.
Cardiovascular Drugs: Experience of the Drug Efficacy Study (DES)
Authors: EDWARD D. FREIS
Journal: Circulation (1970)

PRIOR to 1962 the only legal requirement for marketing a new drug was adequate evidence of safety.The Kefauver-Harris Amendments Act of 1962 altered the original 1938 law to require that valid evidence also must be provided to support the claims of therapeutic efficacy.The FDA, suddenly faced with the task of evaluating the large number of drugs marketed between 1938 and 1962, sought the assistance of the National Research Council.The result was the establishment of the Drug Efficacy Study (DES), in which panels of specialists evaluated the drugs used in their various disciplines.Two of the panels reviewed the cardiovascular drugs marketed between 1938 and 1962 which included approximately 300 products.The great major- ity of these preparations were antihyperten- sive agents of which the bulk were commer- cial products containing crude Rauwolfia serpentina or reserpine.Also included were diuretics, cardiotonics, peripheral vasodilator drugs, long-acting nitrites, miscellaneous agents, and a great variety of drug combina- tions.The experience gained in assessing this large number of pharmaceutical products seemed of sufficient general interest to war- rant the present editorial.Quality of the Evidence for Therapeutic Effectiveness It soon became apparent after reviewing the pertinent literature that many claims of therapeutic effectiveness rested on flimsy evidence.Well-designed, controlled clinical trials were nonexistent in several categories of
Molecular Evolution of a Primate-Specific microRNA Family
Authors: R. Zhang, Y.-Q. Wang, B. Su
Journal: Molecular Biology and Evolution (2008)

Lineage-specific microRNA (miRNA) families may contribute to developmental novelties during evolution. However, little is known about the origin and evolution of new miRNA families. We report evidence of an Alu-mediated rapid expansion of miRNA genes in a previously identified primate-specific miRNA family, drawn from sequencing and comparative analysis of 9 diverse primate species. Evolutionary analysis reveals similar divergence among miRNA copies whether they are within or between species, lineage-specific gain and loss of miRNAs, and gene pseudolization in multiple species. These observations support a birth-and-death process of miRNA genes in this family, implicating functional diversification during primate evolution. In addition, both secondary structure conservation and reduced single nucleotide polymorphisms density attest to functional constraint of this family in primates. Finally, we observed preferential expression of miRNAs in human placenta and fetal brain, suggesting a functional importance of this family for primate development.