tbuckley/cabot-search huggingface dataset:
Stroke and the “Stroke Belt” in Dialysis
Authors: James B. Wetmore, Edward F. Ellerbeck, Jonathan D. Mahnken, Milind A. Phadnis, Sally K. Rigler, John A. Spertus, Xinhua Zhou, Purna Mukhopadhyay, Theresa I. Shireman
Journal: Journal of the American Society of Nephrology (2013)

Geographic variation in stroke rates is well established in the general population, with higher rates in the South than in other areas of the United States. ESRD is a potent risk factor for stroke, but whether regional variations in stroke risk exist among dialysis patients is unknown. Medicare claims from 2000 to 2005 were used to ascertain ischemic stroke events in a large cohort of 265,685 incident dialysis patients. A Poisson generalized linear mixed model was generated to determine factors associated with stroke and to ascertain state-by-state geographic variability in stroke rates by generating observed-to-expected (O/E) adjusted rate ratios for stroke. Older age, female sex, African American race and Hispanic ethnicity, unemployed status, diabetes, hypertension, history of stroke, and permanent atrial fibrillation were positively associated with ischemic stroke, whereas body mass index >30 kg/m(2) was inversely associated with stroke (P<0.001 for each). After full multivariable adjustment, the three states with O/E rate ratios >1.0 were all in the South: North Carolina, Mississippi, and Oklahoma. Regional efforts to increase primary prevention in the "stroke belt" or to better educate dialysis patients on the signs of stroke so that they may promptly seek care may improve stroke care and outcomes in dialysis patients.
Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable GI Stromal Tumor After Failure of Imatinib and Sunitinib: A Multicenter Phase II Trial
Authors: Suzanne George, Qian Wang, Michael C. Heinrich, Christopher L. Corless, Meijun Zhu, James E. Butrynski, Jeffrey A. Morgan, Andrew J. Wagner, Edwin Choy, William D. Tap, Jeffrey T. Yap, Annick D. Van den Abbeele, Judith B. Manola, Sarah M. Solomon, Jonathan A. Fletcher, Margaret von Mehren, George D. Demetri
Journal: Journal of Clinical Oncology (2012)

Purpose Metastatic GI stromal tumor (GIST) is a life-threatening disease with no therapy of proven efficacy after failure of imatinib and sunitinib. Regorafenib is a structurally unique inhibitor of multiple cancer-associated kinases, including KIT and platelet-derived growth factor receptor (PDGFR), with broad-spectrum anticancer activity in preclinical and early-phase trials. Because KIT and PDGFR-α remain drivers of GIST after resistance to imatinib and sunitinib, we performed a multicenter single-stage phase II trial of regorafenib in patients with advanced GIST after failure of at least imatinib and sunitinib. Patients and Methods Patients received regorafenib orally, 160 mg daily, on days 1 to 21 of a 28-day cycle. Disease assessment was performed every two cycles per RECIST 1.1. Primary end point was clinical benefit rate (CBR), defined as objective responses (ie, complete or partial response [PR] as well as stable disease [SD] ≥ 16 weeks). Serial tumor biopsies were obtained from consenting patients whenever possible. Results From February to December 2010, 34 patients were enrolled at four US centers. As of July 28, 2011, 33 patients had received at least two cycles of regorafenib (range, two to 17 cycles). CBR was 79% (95% CI, 61% to 91%). Four patients achieved PR, and 22 exhibited SD ≥ 16 weeks. Median progression-free survival was 10.0 months. The most common grade 3 toxicities were hypertension and hand-foot-skin reaction. Conclusion Regorafenib has significant activity in patients with advanced GIST after failure of both imatinib and sunitinib. A phase III trial of regorafenib versus placebo is ongoing to define more fully the safety and efficacy of regorafenib in this setting.
A Case of Exophthalmic Goitre with New Phenomena
Authors: I. B. Yeo
Journal: BMJ (1877)

following manner.The male infant is well-known to be larger than the female at full term; so that, on the average, the male is ten ounces heavier than the female, while the length is half-an-inch greater.This, perhaps, would not be of so great importance had not the cranium of the male been more completely ossified than that of the female ; so that this, coupled with an increase of circumference, on an average half-an-inch, renders its delivery through a narrow pelvis more difficult than the female's, because of its being less capable of being moulded to a shape easy for passing.In consequence of this, the birth of a male child is more difficult and dangerous to the mother.Sir James Simpson considered the difference-in the sexes of great importance; for he cal- culated that, between the years i834 and i837, in Great Britain, from 46 to 47 per i,ooo male infants lost their lives at birth, owing to the excess of size; and three to four thousand mothers also, from the same cause.This may be overrated, because the calculations were .madefrom the statistics of lying-in hospitals, where a considerable number of difficult cases were admitted in labour for operation ; and thus the foetal death-rate would be increased above the general average.Still, doubtless, after labour, although the child may be born alive, the effects of the difficulty are felt for some time, and many deaths take place in consequence, in a diminishing ratio, for one, two, or even three or four years.Dr. Langdon Down has recently, in a paper read before the Obstetrical Society, shown that, according to his notes, there is a marked preponderance in the number of male over female idiots, in the proportion of 2.I to .9; or rather more than twice as many.He has also noticed that infantile convulsions have occurred among males who have become idiots much more frequently than among females.Dr. Langdon Down attributes these calamities to the increased length and difficulty at the birth of the male by reason of its enlarged cranium, whereby pressure on the circulation produces a kind of asphyxia.He found that first-born children were more frequently afflicted than others ; and, as prolonged and difficult labour generally attended the birth of a first child, he considered it probably the result of the pressure.Exceedingly interesting tables are given by Dr. Collins, of the Rotunda Lying-in Hospital, Dublin, as to the relative death-rate of the sexes shortly after delivery.I will not detain you on this point, but I cannot refrain from quoting the first three lines, which show that, within haf-an-hour after birth, i6 males died against I female ; within the first hour, i9 males died against 2 females ; within the first six hours, 29 males died against 7 females.There can be no doubt, therefore,
Multinational Outbreak of &lt;EMPH TYPE="ITAL"&gt;Salmonella enterica&lt;/EMPH&gt; Serotype Newport Infections Due to Contaminated Alfalfa Sprouts
Authors: Chris A. Van Beneden
Journal: JAMA (1999)

][4][5] In January 1996, public health officials in Oregon and British Columbia independently noted marked increases in reported Salmonella enterica serotype Newport (SN) infections.Routine notification of surrounding states and provinces led to the recognition of this coincidence.The resulting coordinated epidemiologic investigation identified a common source outbreak.Discussions with epidemiologists at the Centers for Disease Control and Prevention (CDC) led to the retrospective identification of a large and previously unexplained outbreak of SN infections affecting the central and eastern United
Phase I Combination Trial of Lenalidomide and Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes
Authors: Mikkael A. Sekeres, Alan F. List, David Cuthbertson, Ronald Paquette, Rebecca Ganetsky, Deborah Latham, Katarina Paulic, Manuel Afable, Hussain I. Saba, Thomas P. Loughran, Jaroslaw P. Maciejewski
Journal: Journal of Clinical Oncology (2010)

Purpose Lenalidomide and azacitidine are active in patients with lower- and higher-risk myelodysplastic syndromes (MDS). These agents may complement each other by targeting both the bone marrow microenvironment and hypomethylating action on the malignant clone. Patients and Methods This phase I trial explored the safety of combination therapy in patients with higher-risk MDS. Response and characterization of molecular and methylation status of responders were secondary objectives. Patients were enrolled using a 3 + 3 dose escalation. Cycles lasted 28 days, and patients received a maximum of seven cycles. Results Of 18 patients enrolled, median age was 68 years (range, 52 to 78 years), interval from diagnosis was 5 weeks (range, 2 to 106 weeks), and follow-up was 7 months (range, 1 to 26 months). International Prognostic Scoring System categories were intermediate 1 (n = 2), intermediate 2 (n = 10), and high (n = 6). No dose-limiting toxicities occurred, and a maximum-tolerated dose was not reached. Grades 3 to 4 nonhematologic toxicities (&gt; 1) included febrile neutropenia (n = 5), cardiac (n = 2), and CNS hemorrhage (n = 2). Median absolute neutrophil count decrease was 26%, and platelet decrease was 1% (mean, 24%). The overall response rate was 67%: eight patients (44%) had a complete response (CR); three patients (17%) had hematologic improvement; one patient (6%) had marrow CR. Patients achieving CR were more likely to have normal cytogenetics and lower methylation levels. Conclusion The combination of lenalidomide and azacitidine is well tolerated with encouraging clinical activity. The go-forward dose is azacitidine 75 mg/m 2 on days 1 through 5 and lenalidomide 10 mg on days 1 through 21.
ENHANCED ERYTHROPOIESIS WITH CONCOMITANT DIMINISHED GRANULOPOIESIS IN PREIRRADIATED RECIPIENT MICE
Authors: Samuel Hellman, Helen E. Grate
Journal: The Journal of Experimental Medicine (1968)

Three different methods of measuring the proliferative capacity of transplanted mouse bone marrow were used to study the effects of preirradiation of the recipient. Recipient mice were exposed to 700 R and given graded numbers of syngeneic bone marrow. 7 days were allowed for proliferation of these cells, and then the granulocytic or erythrocytic progeny was measured. The former was determined by the response to endotoxin, and the latter by the incorporation of radioactive iron into newly formed red blood cells. Erythropoiesis, therefore, could be measured independently from granulopoiesis by these techniques. The third method used was the spleen colony method of Till and McCulloch (5). Recipient animals exposed to 150 R preirradiation, 7 days before 700 R and bone marrow transplantation, demonstrated an increase in erythropoiesis with a concommittant decrease in granulopoiesis compared to similar recipients not preirradiated. The spleen colony technique showed that while the number of colonies were the same in both groups, the colonies themselves were significantly larger in the preirradiated animals. Since such colonies are primarily erythropoietic, this finding is consistent with the other methods. The results can be explained by assuming the presence of a hematopoietic stem cell which, in these preirradiated recipients, is directed towards erythropoiesis at the expense of granulopoiesis.
Busulphan lung: electron microscopy.
Authors: J M Kay
Journal: Thorax (1970)

Environmental insults during sensitive periods can affect hippocampal development and function, but little is known about peripheral infection, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Using a piglet model, the present study showed that inoculation on postnatal day 7 with the porcine reproductive and respiratory syndrome virus (PRRSV) caused microglial activation within the hippocampus with 82% and 43% of isolated microglia being MHC II<sup>+</sup> 13 and 20 d after inoculation, respectively. In control piglets, &lt;5% of microglia isolated from the hippocampus were MHC II<sup>+</sup>. PRRSV piglets were febrile (<i>p</i> &lt; 0.0001), anorectic (<i>p</i> &lt; 0.0001), and weighed less at the end of the study (<i>p</i> = 0.002) compared with control piglets. Increased inflammatory gene expression (e.g., IL-1β, IL-6, TNF-α, and IFN-γ) was seen across multiple brain regions, including the hippocampus, whereas reductions in CD200, NGF, and MBP were evident. In a test of spatial learning, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and had a higher total distance moved. Overall, these data demonstrate that viral respiratory infection is associated with a marked increase in activated microglia in the hippocampus, neuroinflammation, and impaired performance in a spatial cognitive task. As respiratory infections are common in human neonates and infants, approaches to regulate microglial cell activity are likely to be important.
Oxidized-polymers of Z-AT are associated with exaggerated pulmonary inflammation post lung transplantation
Authors: Sam Alam, Karthik Santhanakrishnan, Jas Parmar, Ravi Mahadeva
Journal: European Respiratory Journal (2012)

Z antitrypsin (Z-AT) polymerises in the liver and is associated with early onset emphysema. Z-AT polymers are inactive as antiproteinases. We studied patients with and without Z-AT deficiency who had had a lung transplant for emphysema, to examine the relationship between oxidized-polymers (Ox-pZ-AT) and infection/inflammation. BALF was obtained at scheduled surveillance, and as indicated for infection/rejection and airway injury and, assessed by ELISA and immunoblot using a mAb (3F4) to oxidized AT. BALF cell pellets were lysed and HLE activity was used as a measure of PMN count. 16 patients post-transplant were evaluated, 6 Z-AT (15 samples); 9 infective tracheobronchitis, 3 airway stenosis, 1 reflux, 2 normal, and 10 M-AT (20 samples); 7 infective tracheobronchitis, 8 rejection, 5 normal. The Z-AT group with infection had higher Ox-pZ-AT; 386±85ng/ml mean(SEM), p<0.001 (compared with non-infected Z-AT group, 100±46ng/ml) and confirmed by immunoblot. The Z-AT group had higher free HLE than M-AT, 139(226-102)ng/ml vs. 74(105-46), (Z vs. M), p<0.001. Free HLE in Z-AT was correlated with Ox-pZ-AT levels; R2=0.89. HLE assay of lysed neutrophils showed that the Z-AT group had a higher total PMN count than M-AT; 81±19ng/ml vs. 39±15, p=0.03; infected Z-AT (54±9ng/ml) vs. infected M-AT (31±8), p=0.03. Ox-pZ-AT present in BALF of Z-AT transplanted individuals are associated with excess PMN and, closely correlated with free HLE. Ox-pZ-AT production results in further reduction of the anti-proteinase and anti-inflammatory protection in the lung and leads to PMN influx. This may predispose Z-AT individuals to exaggerated lung destruction and a worse outcome after lung transplantation.
Motivation in tennis
Authors: Miguel Crespo, Machar M Reid
Journal: British Journal of Sports Medicine (2007)

Motivation underpins successful tennis performance, representing one of the game’s foremost psychological skills. This paper elaborates on its role in tennis play, and takes an overview of the current state of motivation research applied to tennis. First, the importance of motivation in player and coach performance is explored. The body of evidence pertaining to players’ motives for participation and the relevance of goal achievement motivation in tennis is then examined. Finally, the efficacy of motivational climates created by significant others is discussed in light of current practice.
Prognostic Significance of CEA, CA19-9 and CA72-4 Serum Level Before and After Preoperative Chemotherapy of Esophagogastric Junction Adenocarcinoma
Authors: Zemanova Milada, Pechačová Zdenka, Haruštiak Tomáš, Fencl Pavel, Vítek Pavel, Petruželka Luboš
Journal: Annals of Oncology (2014)
Angiotensin IV Activates the Nuclear Transcription Factor-κB and Related Proinflammatory Genes in Vascular Smooth Muscle Cells
Authors: Vanesa Esteban, Mónica Ruperez, Elsa Sánchez-López, Juan Rodríguez-Vita, Oscar Lorenzo, Heidi Demaegdt, Patrick Vanderheyden, Jesús Egido, Marta Ruiz-Ortega
Journal: Circulation Research (2005)

Inflammation is a key event in the development of atherosclerosis. Nuclear factor-kappaB (NF-kappaB) is important in the inflammatory response regulation. The effector peptide of the renin angiotensin system Angiotensin II (Ang II) activates NF-kappaB and upregulates some related proinflammatory genes. Our aim was to investigate whether other angiotensin-related peptides, as the N-terminal degradation peptide Ang IV, could regulate proinflammatory factors (activation of NF-kappaB and related genes) in cultured vascular smooth muscle cells (VSMCs). In these cells, Ang IV increased NF-kappaB DNA binding activity, caused nuclear translocation of p50/p65 subunits, cytosolic IkappaB degradation and induced NF-kappaB-dependent gene transcription. Ang II activates NF-kappaB via AT1 and AT2 receptors, but AT1 or AT2 antagonists did not inhibit NF-kappaB activation caused by Ang IV. In VSMC from AT1a receptor knockout mice, Ang IV also activated NF-kappaB pathway. In those cells, the AT4 antagonist divalinal diminished dose-dependently Ang IV-induced NF-kappaB activation and prevented IkappaB degradation, but had no effect on the Ang II response, indicating that Ang IV activates the NF-kappaB pathway via AT4 receptors. Ang IV also increased the expression of proinflammatory factors under NF-kappaB control, such as MCP-1, IL-6, TNF-alpha, ICAM-1, and PAI-1, which were blocked by the AT4 antagonist. Our results reveal that Ang IV, via AT4 receptors, activates NF-kappaB pathway and increases proinflammatory genes. These data indicate that Ang IV possesses proinflammatory properties, suggesting that this Ang degradation peptide could participate in the pathogenesis of cardiovascular diseases.
A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study
Authors: J.J. Biagi, A.M. Oza, H.I. ChalChal, R. Grimshaw, S.L. Ellard, U. Lee, H. Hirte, J. Sederias, S.P. Ivy, E.A. Eisenhauer
Journal: Annals of Oncology (2010)
A case of acute myelogenous leukemia with an 8–21 translocation, missing Y, and additional karyotypic abnormalities
Authors: Yasuhiko Kaneko, Masaharu Sakurai, Masao Hattori
Journal: American Journal of Hematology (1978)

Abstract A patient with acute myelogenous leukemia (AML) whose bone marrow cells had complicated chromosomal abnormalities, in addition to an 8–21 translocation and a missing Y chromosome, is reported. The complex additional abnormalities did not appear to have much influence on the clinical aspects of the disease, eg, cytology of the leukemic cells and the patient's response to chemotherapy, even though the patient did have a rectal tumor due to leukemic cell infiltration.
The <i>let-7</i> MicroRNA Represses Cell Proliferation Pathways in Human Cells
Authors: Charles D. Johnson, Aurora Esquela-Kerscher, Giovanni Stefani, Mike Byrom, Kevin Kelnar, Dmitriy Ovcharenko, Mike Wilson, Xiaowei Wang, Jeffrey Shelton, Jaclyn Shingara, Lena Chin, David Brown, Frank J. Slack
Journal: Cancer Research (2007)

Abstract MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal lung tissue, and that inhibiting let-7 function leads to increased cell division in A549 lung cancer cells. Overexpression of let-7 in cancer cell lines alters cell cycle progression and reduces cell division, providing evidence that let-7 functions as a tumor suppressor in lung cells. let-7 was previously shown to regulate the expression of the RAS lung cancer oncogenes, and our work now shows that multiple genes involved in cell cycle and cell division functions are also directly or indirectly repressed by let-7. This work reveals the let-7 microRNA to be a master regulator of cell proliferation pathways. [Cancer Res 2007;67(16):7713–22]
Myelogenous leukemia evolving during the course of lymphoid malignancy in children
Authors: J. J. Hutter, T. Hays, R. C. Rosen, A. Shende, P. Lanzkowsky, J. J. Corrigan
Journal: American Journal of Hematology (1979)

Abstract Two children who presented initially with a lymphoid malignancy were noted to develop recurrences with myeloid features late in the course of their disease. In both cases, evidence of lymphoid differentiation was present in the myelogenous cells that were Ph1 chromosome negative. The first patient had acute myelogenous leukemia and developed a recurrence with morphologic features of acute myelogenous leukemia. Terminal transferase was present in the myelogenous blasts. The second patient initially had a diffuse lymphoblastic non‐Hodgkin lymphoma. During the course of her illness she developed a myeloproliferative disorder characterized by basophilic meningitis, splenomegaly, and hypereosinophilia. Lymphocyte T‐cell (E‐rosette) markers were present on the eosinophils. These observations lend further support to the hypothesis of varying lymphoid and myeloid differentiation in certain cases of leukemia.
Bone formation in a cutaneous pyogenic granuloma
Authors: R. A. FULTON, G. D. SMITH, J. THOMSON
Journal: British Journal of Dermatology (1980)

Journal Article Bone formation in a cutaneous pyogenic granuloma Get access R. A. FULTON, R. A. FULTON Department of Dermatology, Royal Infirmary, Glasgow G4 0SF Search for other works by this author on: Oxford Academic Google Scholar G. D. SMITH, G. D. SMITH Department of Pathology, Royal Infirmary, Glasgow G4 0SF Search for other works by this author on: Oxford Academic Google Scholar J. THOMSON J. THOMSON Department of Dermatology, Royal Infirmary, Glasgow G4 0SF Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 102, Issue 3, 1 March 1980, Pages 351–352, https://doi.org/10.1111/j.1365-2133.1980.tb08153.x Published: 01 March 1980
Watchdog criticises unequal distribution of NHS funding
Authors: Rebecca Coombes
Journal: BMJ (2004)

A report by independent NHS inspectors has highlighted glaring inequalities in health between rich and poor areas in England and Wales and criticises the low numbers of GPs in deprived areas, which might be expected to need doctors most.

The Healthcare Commission, which has taken over the inspection role of the Commission for Health Improvement, said that the most deprived communities were still not being funded in line with their needs, despite a government formula designed to do just that.

Inspectors found that the 2002 formula for assessing health needs—the PCT [primary care trust] revenue resource limits—was not being phased in quickly enough because the government feared the reaction from affluent areas as funds were withdrawn and redistributed to poorer districts.

For historical reasons, Easington Primary Care Trust, County …