tbuckley/cabot-search huggingface dataset:
Abstract P1-16-01: Skeletal-related events (SRE) prevented in breast cancer patients with bone metastases in the United States (US)
Authors: J Arellano, K Chen, M Halperin, M Danese
Journal: Cancer Research (2013)

Abstract Background: SREs are potentially debilitating consequences of bone metastases in advanced stage cancers. Bone-targeting agents (BTAs), including denosumab and intravenous zoledronic acid (ZA) are approved to prevent SREs. The purpose of this study was to estimate the annual number of SREs that might occur in US women with breast cancer without intervention, and to estimate the SREs that could be prevented with denosumab or with ZA. Methods: A model was developed using US prevalence estimates (Li, et al. 2011), combined with 2012 Census projections to estimate the number of SREs in women with bone metastases from breast cancer in 2012. SREs were defined as fracture, radiation to bone, surgery to bone, or spinal cord compression. The SRE rate in untreated patients was estimated by pooling rates from 8 treatment groups in 4 trials (Lipton 2000; Rosen 2003; Kohno 2005; Stopeck 2010), applying the appropriate relative hazard (RH) of first and subsequent SRE from a network meta-analysis (NMA;Ford 2012), and weighting by the sample size. The denosumab and ZA SRE rates were derived from the pooled rate and the RH estimates from the NMA. Ineligibility was defined as one of the following: all uninsured patients (US Census) and patients discontinuing due to adverse events or non-compliance (ZA 4.6%, denosumab 3.7%; Stopeck 2010). Patients with kidney clearance &amp;lt; 30 ml/min (1.3%; Launay-Vacher 2007) were considered ineligible to receive ZA. Using Monte Carlo sampling, we derived mean estimates and 95% simulation intervals (SI) based on 1,000 samples. Results: Overall, we estimated 96,598 women with breast cancer had bone metastases at any given time in 2012. We estimated 164,673 (95% SI 110,153 to 220,770) SREs would have occurred in 2012 if no women were treated. Assuming all women eligible to receive ZA were treated with ZA (n = 83,870), the number of SREs would have been 108,233 (decline of 56,440, 95% SI 13,744 to 100,098); assuming all women eligible to received denosumab were treated with denosumab (n = 85,780), the number of SREs would have been 86,992 (decline of 77,681, 95% SI 38,327 to 120,521). The incremental difference between denosumab and ZA was 21,242 (95% SI 9,312 to 36,674). Conclusions: The use of BTAs to reduce SRE risk, including denosumab, could result in reductions in the number of adverse skeletal complications in the US. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-16-01.
Postexercise Ischemia Is Associated With Increased Neuropeptide Y in Patients With Coronary Artery Disease
Authors: Lars Gullestad, Bjørn Jørgensen, Thorvald Bjurø, John Pernow, Jan M. Lundberg, Corina-Dana Dota, Christian Hall, Svein Simonsen, Bengt Åblad
Journal: Circulation (2000)

Background —Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. Methods and Results —Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was −223±20.2 μV ( P &lt;0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (−49±8.9 μV, P &lt;0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was −6.0±0.77 μV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST “deficit.” Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise ( r =−0.61, P =0.0005), the ST deficit at the corresponding time point ( r =−0.66, P =0.0001), and the duration of ST-segment depression after exercise ( r =0.42, P =0.02). In contrast, no such correlations were found for NE. Conclusions —The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.
THE STATUS OF RADIOLOGY
Authors: ARTHUR U. DESJARDINS
Journal: JAMA (1931)

The discovery of roentgen rays and radium came at a time when the development of surgery, made possible by the revelations of Pasteur and their successful application by Lister, was in full swing. It is but natural, therefore, that the first utilization of the discovery should have been in relation to surgery. Moreover, since the most striking feature of roentgen rays is their power to penetrate tissues in proportion to their density, it is not surprising that surgeons should have realized the significance of this new and invaluable method of studying the skeleton and its diseases. For a short time such investigation occupied medical attention exclusively and led to observations which amazed equally physicians and the public. Within a few months, however, it became obvious that, besides the uncanny property of traversing tissues and affecting the sensitive emulsion of a photographic plate, the rays also had a potent and destructive
Veganism: A Clinical Survey with Observations on Vitamin-B12 Metabolism
Authors: A. D. M. Smith
Journal: BMJ (1962)

DIET AND BLOOD COAGULATION BrOUr 1655 blood coagulation were most active and platelet survival shortest when the diet was rich in dairy fats and eggs.When t-he diet contained little fat converse results were obtained.A diet rich in vegetable fat produced inter- mediate results.The serum cholesterol and phospho- lipid values were highest with the dairy fat and egg yolk diet.However, poor correlations were fou-nd between the level of the blood lipids and the coagulation tests.Thus, extended studies have shown that dietary control influences not only serum lipid values but also blood coagulation in vitro and platelet economy in vivo.
The Great White Lie: How America's Hospitals Betray Our Trust and Endanger Our Lives
Authors: George Ross Fisher
Journal: JAMA (1992)

A lurid title, an offensive subtitle, and an inflammatory picture on the jacket all announce that describing this book as yellow journalism might be to flatter it. Furthermore, the very first sentence reads "Kathryn Hinnant began the last day of her life making love." It is therefore difficult for a reviewer to make a balanced comment about the serious problems that the author more or less describes. However, among others, they are the following: Hospital care has grown so much more complex so rapidly that systems of management and supervision have had difficulty adjusting to the changing environment. In particular, the greatly increased numbers of hospital employees have not all been appropriately trained, particularly when there are local shortages of them. New techniques have had to be implemented when there existed only a scanty base of experience upon which to base protocols and standards. For reasons both practical and political,
Chronic pancreatitis is associated with increased concentrations of epidermal growth factor receptor, transforming growth factor alpha, and phospholipase C gamma.
Authors: M Korc, H Friess, Y Yamanaka, M S Kobrin, M Buchler, H G Beger
Journal: Gut (1994)

The epidermal growth factor (EGF) receptor is a transmembrane protein that binds EGF and transforming growth factor alpha (TGF alpha), and that stimulates phospholipase C gamma 1 (PLC gamma 1) activity. In this study the role of the EGF receptor in chronic pancreatitis was studied. By immunohistochemistry, the EGF receptor, TGF alpha, and PLC gamma 1 were found to be expressed at high concentrations in pancreatic ductal and acinar cells from chronic pancreatitis patients. Northern blot analysis showed that, by comparison with normal controls, 19 of 27 chronic pancreatitis tissues exhibited a 5.7-fold increase in EGF receptor mRNA concentrations, and 20 of 27 chronic pancreatitis tissues exhibited a sixfold increase in TGF alpha mRNA concentrations. In situ hybridisation confirmed that overexpression occurred in ductal and acinar cells, and showed that both mRNA moieties colocalised with their respective proteins. These findings suggest that TGF alpha may act through autocrine and paracrine mechanisms to excessively activate the overexpressed EGF receptor in the two major cell types of the exocrine pancreas, thereby contributing to the pathobiology of this disorder.
High-dose methotrexate for elderly patients with primary CNS lymphoma
Authors: Jay-Jiguang Zhu, Elizabeth R. Gerstner, David A. Engler, Maciej M. Mrugala, Whitney Nugent, Kristin Nierenberg, Fred H. Hochberg, Rebecca A. Betensky, Tracy T. Batchelor
Journal: Neuro-Oncology (2008)

The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL.
Juxtaposition of Atrial Appendages Associated with Normally Oriented Ventricles and Great Arteries
Authors: ANTON E. BECKER, MIES J. BECKER
Journal: Circulation (1970)

A case is reported of a stillborn infant in whom both atrial appendages lay to one side of the great arteries, so-called juxtaposition of the atrial appendages. The unusual features of the case reported are twofold. First, both atrial appendages lay to the right of the great vessels while, more commonly, juxtaposed atrial appendages lie to the left of the aorta and pulmonary trunk. Second, in our case the great vessels were normally related and no major intracardiac malformations were present (only an atrial septal defect and a bicuspid pulmonary valve), while, more commonly, the great vessels are transposed and major intracardiac malformations are associated.
Letter: Breast cancer in young women.
Authors: D W Charters
Journal: BMJ (1975)

between the ulcer and the cardiac orifice.The ulcer was irregular in shape with a 1-cm proximal lesion on the anterior wall and a distal 4-cm lesion imme- diately below it which encircled most of the oesophagus and which communicated with the aorta through a channel 0-3 cm in diameter.It was thought that the entrance to the aorta was at the site of an intercostal vessel which had been involved in the ulcer base.There were adhesions between the aorta and the oesophagus.Altered blood was present which was adherent to the ulcer base and the stomach contained a cast of clot.No radio- graphs of the oesophagus were available.At necropsy the ulcerated area appeared to occupy the midline.
HEMOGLOBIN AND PLASMA PROTEIN PRODUCTION
Authors: F. S. Robscheit-Robbins, L. L. Miller, G. H. Whipple
Journal: The Journal of Experimental Medicine (1946)

Given healthy dogs, fed abundant iron and protein-free or low protein diets, with sustained anemia and hypoproteinemia due to bleeding, we can study the capacity of these animals to produce simultaneousiy new hemoglobin and plasma protein. The reserve stores of blood protein-producing materials in this way are largely depleted, and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for considerable periods of time. These dogs are very susceptible to infection and to injury by many poisons. Dogs tire of these diets and loss of appetite terminates many experiments. These incomplete experiments are not recorded in the present paper but give supporting evidence in harmony with those tabulated. Under these conditions (double depletion) the dogs use effectively the proteins listed above-egg, lactalbumin, meat, beef plasma, and digests of various food proteins and hemoglobin. Egg protein at times seems to favor slightly the production of plasma protein when compared with the average response (Tables 1 and 2). Various digests and concentrates compare favorably with good food proteins in the production of new hemoglobin and plasma protein in these doubly depleted dogs. Whole beef plasma by mouth is well utilized and the production of new hemoglobin is, if anything, above the average-certainly plasma protein production is not especially favored. "Modified" beef plasma by vein causes fatal anaphylaxis (Table 4). Hemoglobin digests are well used by mouth to form both hemoglobin and plasma protein. Supplementation by amino acids is recorded. Methionine in one experiment may have been responsible for a better protein output and digest utilization (Table 7).
Angiotensin-Converting Enzyme Inhibitor Ramiprilat Interferes With the Sequestration of the B <sub>2</sub> Kinin Receptor Within the Plasma Membrane of Native Endothelial Cells
Authors: Thomas Benzing, Ingrid Fleming, Andree Blaukat, Werner Müller-Esterl, Rudi Busse
Journal: Circulation (1999)

Background —ACE (kininase II) inhibitors have been shown to exert their beneficial cardiovascular effects via the inhibition of both angiotensin II formation and bradykinin breakdown. Because recent evidence suggests that ACE inhibitors may also interfere with B 2 kinin receptor signaling and thus enhance the vascular response to bradykinin, we examined whether the distribution of B 2 kinin receptors within the plasma membrane of native endothelial cells is affected by an ACE inhibitor. Methods and Results —Localization of the B 2 kinin receptor in membranes prepared from native porcine aortic endothelial cells was evaluated by means of specific [ 3 H]bradykinin binding and immunoprecipitation of the B 2 receptor from isolated membranes. Effects of bradykinin and ramiprilat on intracellular signaling were determined by monitoring the activation of the extracellularly regulated kinases Erk1 and Erk2 as well as [Ca 2+ ] i increases in fura 2–loaded endothelial cells. Stimulation of native endothelial cells with bradykinin 100 nmol/L resulted in the time-dependent sequestration of the B 2 receptor to caveolin-rich (CR) membranes, which was maximal after 5 minutes. Pretreatment with ramiprilat 100 nmol/L for 15 minutes significantly attenuated the recovery of B 2 kinin receptors in CR membranes while increasing that from membranes lacking caveolin. This effect was not due to the inhibition of bradykinin degradation, because no effect was seen in the presence of an inhibitory concentration of the synthetic ACE substrate hippuryl- l -histidyl- l -leucine. Ramiprilat also decreased [ 3 H]bradykinin binding to CR membranes when applied either before or after bradykinin stimulation. Moreover, ramiprilat resulted in reactivation of the B 2 receptor in bradykinin-stimulated cells and induced a second peak in [Ca 2+ ] i and reactivation of Erk1/2. Conclusions —The ACE inhibitor ramiprilat interferes with the targeting of the B 2 kinin receptor to CR membrane domains in native endothelial cells. Therefore, effects other than the inhibition of kininase II may account for the effects of ramiprilat and other ACE inhibitors on the vascular system.
The artful mind meets art history: Toward a psycho-historical framework for the science of art appreciation
Authors: Nicolas J. Bullot, Rolf Reber
Journal: Behavioral and Brain Sciences (2013)

Abstract Research seeking a scientific foundation for the theory of art appreciation has raised controversies at the intersection of the social and cognitive sciences. Though equally relevant to a scientific inquiry into art appreciation, psychological and historical approaches to art developed independently and lack a common core of theoretical principles. Historicists argue that psychological and brain sciences ignore the fact that artworks are artifacts produced and appreciated in the context of unique historical situations and artistic intentions. After revealing flaws in the psychological approach, we introduce a psycho-historical framework for the science of art appreciation . This framework demonstrates that a science of art appreciation must investigate how appreciators process causal and historical information to classify and explain their psychological responses to art. Expanding on research about the cognition of artifacts, we identify three modes of appreciation: basic exposure to an artwork, the artistic design stance , and artistic understanding . The artistic design stance, a requisite for artistic understanding, is an attitude whereby appreciators develop their sensitivity to art-historical contexts by means of inquiries into the making, authorship, and functions of artworks. We defend and illustrate the psycho-historical framework with an analysis of existing studies on art appreciation in empirical aesthetics. Finally, we argue that the fluency theory of aesthetic pleasure can be amended to meet the requirements of the framework. We conclude that scientists can tackle fundamental questions about the nature and appreciation of art within the psycho-historical framework.
Abstract 2817: The contribution of bone marrow cells to carcinogenesis in the chronic inflammatory lung conditions.
Authors: Sachiko Takikawa, Charles Powell
Journal: Cancer Research (2013)

Abstract The role of inflammation in lung carcinogenesis is suggested by the independent association between chronic obstructive lung disease, a systemic inflammatory process, and lung cancer risk. To investigate that chronic inflammation in the lung potentiates tobacco smoke-induced lung carcinogenesis, we utilized two murine models of chronic lung inflammation: a model of sustained intranasal exposure to lipopolysaccharide (LPS) and a transgenic model of inducible interleukin-1β overexpression in the lung. In preliminary experiments, nicotine-derived nitrosamine (NNK) tobacco carcinogen induced tumor multiplicity is significantly increased in stress markers in the lung tumors with chronic inflammation. To determine the role of bone marrow-derived stem cells (BMDCs) in mediating the oxidative stress response in this model of chronic lung inflammation, we performed lineage tracing experiments. BMDCs are capable of self-renewal and recruited to the end organs where they differentiate into various terminal cells. In inflammation-associated gastric cancer, BMDCs contribute to the tumor microenvironment both by direct proliferation of epithelial cells and by differentiation into α-SMA positive cancer-associated fibroblasts. We hypothesize that BMDCs are recruited to inflammatory sites and contribute to the process of lung carcinogenesis through differentiation. We performed bone marrow transplantation from male GFP tagged donors to female chronic lung inflammation models. We investigated the localization and quantification of BMDCs contributions to subsequent lung tumors by immunohistochemistry of GFP and FISH for the Y chromosome. Additionally, we examined the differentiation of BMDCs in the tumor and associated microenvironment. This study has the potential to identify novel pathways of lung carcinogenesis in cigarette carcinogen-induced lung cancers arising in the setting of chronic inflammation. Citation Format: Sachiko Takikawa, Charles Powell. The contribution of bone marrow cells to carcinogenesis in the chronic inflammatory lung conditions. [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 2817. doi:10.1158/1538-7445.AM2013-2817
The Medical Implications of Nuclear War
Authors: Gordon K. MacLeod
Journal: JAMA (1987)

The studies generated in this five-part volume provide a set of truly remarkable insights into the devastation and destruction from nuclear war as told by groups of scientifically oriented physicians and other researchers. The subjects range from atmospheric physics to medical supply and demand in a post—nuclear war world. The highly commendable combination of both natural and social science research leads the reader to the only possible conclusion of strong opposition to nuclear warfare.  On the one hand, the wealth of data available on the biomedical, biosocial, biochemical, and biophysical aspects of nuclear warfare is a revelation in itself. The tone of the volume leaves little doubt about the sincerity of the authors; likewise, the clarity of presentation leaves little doubt about the outcome of nuclear war. Dr Herbert Abrams' concluding summary is masterful, and his epilogue could just as well be prologue: it poses appropriate questions, maps out what
Preparedness for Bioterrorism?
Authors: Hillel W. Cohen, Victor W. Sidel, Robert M. Gould
Journal: New England Journal of Medicine (2001)

To the Editor: Drs. Khan and Ashford, in their editorial (July 26 issue),1 argue that the case of glanders in a microbiologist working in a military laboratory, reported by Srinivasan et al. in the...